Novel 1,2-dihydroquinoline derivative having substituted phenylamino lower alkyl group and ester-introduced phenyl group as substituents

ABSTRACT

The compounds represented in general formula (1) and a salt thereof are useful for glucocorticoid receptor modulator. 
     
       
         
         
             
             
         
       
     
     The R 1  represents a hydrogen atom or a lower alkyl group; R 2  represents a hydrogen atom or a lower alkyl group; R 3  and R 4  may be the same or different and represents a hydrogen atom or a lower alkyl group; R 5  represents a hydrogen atom or a lower alkyl group; R 6  represents a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group, a nitro group or a cyano group; X represents —C(O)—, —C(O)NR 8 —, —S(O) 2 — and the like; R 7  and/or R 8  may be the same or different and represent a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent, a heterocyclic group which may have a substituent, a lower alkoxy group which may have a substituent and the like; Y represents a lower alkylene group; and P represents 0, 1, 2 or 3.

TECHNICAL FIELD

The present invention relates to novel 1,2-dihydroquinoline derivativeshaving substituted phenylamino lower alkyl group and ester-introducedphenyl group as substituents or a salt thereof, which are useful aspharmaceuticals. The derivatives have a glucocorticoid receptor bindingactivity and are useful as glucocorticoid receptor modulators having anonsteroidal structure (glucocorticoid receptor agonists and/orglucocorticoid receptor antagonists).

BACKGROUND ART

A glucocorticoid receptor is a 94 kDa ligand-activated intracellulartranscriptional regulatory factor that is a member of the nuclearreceptor superfamily. This receptor is known to affect the regulation ofthe metabolism of carbohydrates, proteins, fats and the like,suppression of the immune or inflammatory responses, activation of thecentral nervous system, regulation of cardiovascular function, and basaland stress-related homeostasis and the like due to its transcriptionalregulatory action. As diseases which are considered to be related toglucocorticoid receptor, metabolic disorders such as diabetes andobesity, inflammatory diseases such as enteritis and chronic obstructivepulmonary diseases, autoimmune diseases such as connective tissuediseases, allergic diseases such as asthma, atopic dermatitis andallergic rhinitis, central nervous system diseases such as psychiatricdisorders, Alzheimer's disease and drug use disorders, cardiovasculardiseases such as hypertension, hypercalcemia, hyperinsulinemia andhyperlipidemia, homeostasis-related diseases causing an abnormality ofneuro-immune-endocrine balance, glaucoma and the like are known (SOUGOURINSYOU, 54(7), 1951-2076 (2005), JP-A-2002-193955). Therefore, acompound having a glucocorticoid receptor binding activity is useful asa preventive and/or therapeutic agent for these diseases.

As such a compound having a glucocorticoid receptor binding activity,glucocorticoid receptor agonists synthesized in the living body such ascortisol and corticosterone, synthetic glucocorticoid receptor agonistssuch as dexamethasone, prednisone and prednisilone, non-selectiveglucocorticoid receptor antagonists such as RU486 and the like are known(JP-A-2002-193955).

On the other hand, compounds having a 1,2-dihydroquinoline structure aredisclosed as steroid receptor modulators in WO 2004/018429,JP-T-10-0510840, WO 2006/019716 and the like. In WO 2004/018429,JP-T-10-0510840 and WO 2006/019716, many compounds which have very broadand a variety of chemical structures are disclosed, and1,2-dihydroquinoline structure is disclosed as one of them. However,1,2-dihydroquinoline derivatives having substituted phenylamino loweralkyl group and ester-introduced phenyl group as substituents have notbeen specifically disclosed at all.

DISCLOSURE OF THE INVENTION Problems to be Solved

It is a very interesting subject to study the synthesis of novel1,2-dihydroquinoline derivatives having substituted phenylamino loweralkyl group and ester-introduced phenyl group as substituents and a saltthereof, and to find a pharmacological action of the derivatives and asalt thereof.

Means of Solving Problems

The present inventors conducted studies of the synthesis of novel1,2-dihydroquinoline derivatives having substituted phenylamino loweralkyl group and ester-introduced phenyl group as substituents and a saltthereof having a novel chemical structure, and succeeded in producing alarge number of novel compounds.

These novel compounds have chemical structural features 1) to 3) shownin below.

1) Having an ester structure (X is —C(O)—, —C(O)NR⁸—, —S(O)— or —S(O)₂—)in A part of the general formula (1).

2) Having a hydroxy group or a lower alkoxy group in B part of thegeneral formula (1).

3) Having a substituted phenylamino lower alkyl group (Y is a loweralkylene group) in C part of the general formula (1).

Further, as a result of the study about the pharmacological actions ofthe novel compound, the present inventors found that the novel compoundhave a glucocorticoid receptor binding activity and are useful aspharmaceuticals, and thus the present invention has been completed.

That is, the present invention relates to compounds represented by thefollowing general formula (1) or a salt thereof (hereinafter referred toas “the present compound”) and a pharmaceutical composition containingthe same. Further, a preferred invention in its pharmaceutical userelates to glucocorticoid receptor modulators, and its target diseasesare considered to be glucocorticoid receptor-related diseases, that is,metabolic disorders such as diabetes and obesity, inflammatory diseasessuch as enteritis and chronic obstructive pulmonary diseases, autoimmunediseases such as connective tissue diseases, allergic diseases such asasthma, atopic dermatitis and allergic rhinitis, central nervous systemdiseases such as psychiatric disorders, Alzheimer's disease and drug usedisorders, cardiovascular diseases such as hypertension, hypercalcemia,hyperinsulinemia and hyperlipidemia, homeostasis-related diseasescausing an abnormality of neuro-immune-endocrine balance, glaucoma andthe like, and an invention relating to a preventive or a therapeuticagent for these diseases is particularly preferred.

[R¹ represents a hydrogen atom or a lower alkyl group;

R² represents a hydrogen atom or a lower alkyl group;

R³ and R⁴ may be the same or different and represent a hydrogen atom ora lower alkyl group;

R⁵ represents a hydrogen atom or a lower alkyl group;

R⁶ represents a halogen atom, a lower alkyl group, a hydroxy group, alower alkoxy group, a nitro group or a cyano group;

X represents —C(O)—, —C(O)NR⁸—, —S(O)— or —S(O)₂—;

R⁷ and/or R⁸ may be the same or different and represent a hydrogen atom,a lower alkyl group which may have a substituent, a lower alkenyl groupwhich may have a substituent, a lower alkynyl group which may have asubstituent, a lower cycloalkyl group which may have a substituent, anaryl group which may have a substituent, a heterocyclic group which mayhave a substituent, a lower alkoxy group which may have a substituent, alower alkenyloxy group which may have a substituent, a lower alkynyloxygroup which may have a substituent, a lower cycloalkyloxy group whichmay have a substituent, an aryloxy group which may have a substituent ora heterocyclic oxy group which may have a substituent;

Y represents a lower alkylene group;

p represents 0, 1, 2 or 3, in the case where p is 2 or 3, each R⁶ may bethe same or different. Hereinafter the same shall apply.]

ADVANTAGE OF THE INVENTION

The present invention provides novel 1,2-dihydroquinoline derivativeshaving substituted phenylamino lower alkyl group and ester-introducedphenyl group as substituents or a salt, which are useful aspharmaceuticals. The present compound has an excellent glucocorticoidreceptor binding activity and is useful as a glucocorticoid receptormodulator. In particular, the present compound is useful as a preventiveor therapeutic agent for glucocorticoid receptor-related diseases, thatis, metabolic disorders such as diabetes and obesity, inflammatorydiseases such as enteritis and chronic obstructive pulmonary diseases,autoimmune diseases such as connective tissue diseases, allergicdiseases such as asthma, atopic dermatitis and allergic rhinitis,central nervous system diseases such as psychiatric disorders,Alzheimer's disease and drug use disorders, cardiovascular diseases suchas hypertension, hypercalcemia, hyperinsulinemia and hyperlipidemia,homeostasis-related diseases causing an abnormality ofneuro-immune-endocrine balance, glaucoma and the like.

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, definitions of terms and phrases (atoms, groups and thelike) used in this specification will be described in detail. Inaddition, when the definition of terms and phrases is applied to thedefinition of another terms and phrases, a desirable range and theparticularly desirable range of each definition is also applied.

The “halogen atom” refers to a fluorine, chlorine, bromine or iodineatom.

The “lower alkyl group” refers to a straight chain or branched alkylgroup having 1 to 8 carbon atoms, preferably 1 to 6, especiallypreferably 1 to 4. Specific examples thereof include methyl, ethyl,n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, isopropyl,isobutyl, sec-butyl, tert-butyl and isopentyl groups and the like.

The “lower alkenyl group” refers to a straight chain or branched alkenylgroup having 2 to 8 carbon atoms, preferably 2 to 6, especiallypreferably 2 to 4. Specific examples thereof include vinyl, propenyl,butenyl, pentenyl, hexenyl, heptenyl, octenyl, isopropenyl,2-methyl-1-propenyl and 2-methyl-2-butenyl groups and the like.

The “lower alkynyl group” refers to a straight chain or branched alkynylgroup having 2 to 8 carbon atoms, preferably 2 to 6, especiallypreferably 2 to 4. Specific examples thereof include ethynyl, propynyl,butynyl, pentynyl, hexynyl, heptynyl, octynyl, isobutynyl andisopentynyl groups and the like.

The “lower cycloalkyl group” refers to a cycloalkyl group having 3 to 10carbon atoms, preferably 3 to 8, especially preferably 3 to 6. Specificexamples thereof include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, cyclononanyl and cyclodecanylgroups.

The “aryl group” refers to a residue formed by removing one hydrogenatom from a monocyclic aromatic hydrocarbon group, or bicyclic ortricyclic condensed polycyclic aromatic hydrocarbon having 6 to 14carbon atoms. Specific examples thereof include phenyl, naphthyl,anthryl and phenanthryl groups and the like.

The “heterocyclic ring” refers to a saturated or unsaturated monocyclicheterocyclic ring having one or a plurality of heteroatoms selected froma nitrogen atom, an oxygen atom and a sulfur atom in the ring(preferably, a saturated or unsaturated monocyclic 5 or 6 memberedheterocyclic ring having one or two heteroatoms and 3 to 5 carbon atomsin the ring), or a bicyclic or tricyclic condensed polycyclicheterocyclic ring (preferably, a bicyclic or tricyclic condensedpolycyclic heterocyclic ring having one or two heteroatoms and 7 to 13carbon atoms in the ring).

Specific examples of the “saturated monocyclic heterocyclic ring”include pyrrolidine, pyrazolidine, imidazolidine, triazolidine,piperidine, hexahydropyridazine, hexahydropyrimidine, piperazine,homopiperidine and homopiperazine rings and the like having at least anitrogen atom in the ring, tetrahydrofuran and tetrahydropyran rings andthe like having at least an oxygen atom in the ring, tetrahydrothiopheneand tetrahydrothiopyran rings and the like having a sulfur atom in thering, oxazolidine, isoxazolidine and morpholine rings and the likehaving a nitrogen atom and an oxygen atom in the ring, and thiazolidine,isothiazolidine and thiomorpholine rings and the like having a nitrogenatom and a sulfur atom in the ring.

Further, such a saturated monocyclic heterocyclic ring can be condensedwith a benzene ring or the like to form a bicyclic or tricycliccondensed polycyclic heterocyclic ring such as a dihydroindole,dihydroindazole, dihydrobenzimidazole, tetrahydroquinoline,tetrahydroisoquinoline, tetrahydrocinnoline, tetrahydrophthalazine,tetrahydroquinazoline, tetrahydroquinoxaline, dihydrobenzofuran,dihydroisobenzofuran, chromane, isochromane, dihydrobenzothiophene,dihydroisobenzothiophene, thiochromane, isothiochromane,dihydrobenzoxazole, dihydrobenzisoxazole, dihydrobenzoxazine,dihydrobenzothiazole, dihydrobenzisothiazole, dihydrobenzothiazine,xanthene, 4a-carbazole, or perimidine ring and the like.

Specific examples of the “unsaturated monocyclic heterocyclic ring”include dihydropyrrole, pyrrole, dihydropyrazole, pyrazole,dihydroimidazole, imidazole, dihydrotriazole, triazole,tetrahydropyridine, dihydropyridine, pyridine, tetrahydropyridazine,dihydropyridazine, pyridazine, tetrahydropyrimidine, dihydropyrimidine,pyrimidine, tetrahydropyrazine, dihydropyrazine and pyrazine rings andthe like having at least a nitrogen atom in the ring, dihydrofuran,furan, dihydropyran and pyran rings and the like having at least anoxygen atom in the ring, dihydrothiophene, thiophene, dihydrothiopyranand thiopyran rings and the like having a sulfur atom in the ring,dihydrooxazole, oxazole, dihydroisoxazole, isoxazole, dihydrooxazine andoxazine rings and the like having a nitrogen atom and an oxygen atom inthe ring, dihydrothiazole, thiazole, dihydroisothiazole, isothiazole,dihydrothiazine and thiazine rings and the like having a nitrogen atomand a sulfur atom in the ring.

Further, such an unsaturated monocyclic heterocyclic ring can becondensed with a benzene ring or the like to form a bicyclic ortricyclic condensed polycyclic heterocyclic ring such as an indole,indazole, benzimidazole, benzotriazole, dihydroquinoline, quinoline,dihydroisoquinoline, isoquinoline, phenanthridine, dihydrocinnoline,cinnoline, dihydrophthalazine, phthalazine, dihydroquinazoline,quinazoline, dihydroquinoxaline, quinoxaline, benzofuran, isobenzofuran,chromene, isochromene, benzothiophene, isobenzothiophene, thiochromene,isothiochromene, benzoxazole, benzisoxazole, benzoxazine, benzothiazole,benzisothiazole, benzothiazine, phenoxanthin, carbazole, β-carboline,phenanthridine, acridine, phenanthroline, phenazine, phenothiazine orphenoxazine ring and the like.

Incidentally, among the above “heterocyclic ring”, “monocyclicheterocyclic ring” is defined as the thing which put saturatedmonocyclic heterocyclic ring and unsaturated monocyclic heterocyclicring together.

The “heterocyclic group” refers to a residue formed by removing ahydrogen atom from heterocyclic ring mentioned above.

The “lower alkoxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a lower alkyl group. Specificexamples thereof include methoxy, ethoxy, n-propoxy, n-butoxy,n-pentoxy, n-hexyloxy, n-heptyloxy, n-octyloxy, isopropoxy, isobutoxy,sec-butoxy, tert-butoxy and isopentoxy groups and the like.

The “lower alkenyloxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a lower alkenyl group. Specificexamples thereof include vinyloxy, propenyloxy, butenyloxy, pentenyloxy,hexenyloxy, heptenyloxy, octenyloxy, isopropenyloxy,2-methyl-1-propenyloxy and 2-methyl-2-butenyloxy groups and the like.

The “lower alkynyloxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a lower alkynyl group. Specificexamples thereof include ethynyloxy, propynyloxy, butynyloxy,pentynyloxy, hexynyloxy, heptynyloxy, octynyloxy, isobutynyloxy andisopentynyloxy groups and the like.

The “lower cycloalkyloxy group” refers to a group formed by replacingthe hydrogen atom of a hydroxy group with a lower cycloalkyl group.Specific examples thereof include cyclopropyloxy, cyclobutyloxy,cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy,cyclononanyloxy and cyclodecanyloxy groups.

The “aryloxy group” refers to a group formed by replacing the hydrogenatom of a hydroxy group with an aryl group. Specific examples thereofinclude phenoxy, naphthoxy, anthryloxy and phenanthryloxy groups and thelike.

The “heterocyclic oxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with a heterocyclic group.

The “lower alkylthio group” refers to a group formed by replacing thehydrogen atom of a mercapto group with a lower alkyl group. Specificexamples thereof include methylthio, ethylthio, n-propylthio,n-butylthio, n-pentylthio, n-hexylthio, n-heptylthio, n-octylthio,isopropylthio, isobutylthio, sec-butylthio, tert-butylthio andisopentylthio groups and the like.

The “lower alkenylthio group” refers to a group formed by replacing thehydrogen atom of a mercapto group with a lower alkenyl group. Specificexamples thereof include vinylthio, propenylthio, butenylthio,pentenylthio, hexenylthio, heptenylthio, octenylthio, isopropenylthio,2-methyl-1-propenylthio and 2-methyl-2-butenylthio groups and the like.

The “lower alkynylthio group” refers to a group formed by replacing thehydrogen atom of a mercapto group with a lower alkynyl group. Specificexamples thereof include ethynylthio, propynylthio, butynylthio,pentynylthio, hexynylthio, heptynylthio, octynylthio, isobutynylthio andisopentynylthio groups and the like.

The “lower cycloalkylthio group” refers to a group formed by replacingthe hydrogen atom of a mercapto group with a lower cycloalkyl group.Specific examples thereof include cyclopropylthio, cyclobutylthio,cyclopentylthio, cyclohexylthio, cycloheptylthio and cyclooctylthiogroups.

The “arylthio group” refers to a group formed by replacing the hydrogenatom of a mercapto group with an aryl group. Specific examples thereofinclude phenylthio, naphthylthio, anthrylthio and phenanthrylthio groupsand the like.

The “heterocyclic thio group” refers to a group formed by replacing thehydrogen atom of a mercapto group with a heterocyclic group.

The “lower alkylcarbonyl group” refers to a group formed by replacingthe hydrogen atom of a formyl group with a lower alkyl group. Specificexamples thereof include methylcarbonyl, ethylcarbonyl,n-propylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl, n-hexylcarbonyl,n-heptylcarbonyl, n-octylcarbonyl, isopropylcarbonyl, isobutylcarbonyl,sec-butylcarbonyl, tert-butylcarbonyl and isopentylcarbonyl groups andthe like.

The “arylcarbonyl group” refers to a group formed by replacing thehydrogen atom of a formyl group with an aryl group. Specific examplesthereof include phenylcarbonyl, naphthylcarbonyl, anthrylcarbonyl andphenanthrylcarbonyl groups and the like.

The “lower alkoxycarbonyl group” refers to a group formed by replacingthe hydrogen atom of a formyl group with a lower alkoxy group. Specificexamples thereof include methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, n-butoxycarbonyl, n-pentoxycarbonyl,n-hexyloxycarbonyl, n-heptyloxycarbonyl, n-octyloxycarbonyl,isopropoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl,tert-butoxycarbonyl and isopentoxycarbonyl groups and the like.

The “aryloxycarbonyl group” refers to a group formed by replacing thehydrogen atom of a formyl group with an aryloxy group. Specific examplesthereof include phenoxycarbonyl, naphthoxycarbonyl, anthryloxycarbonyland phenanthryloxycarbonyl groups and the like.

The “lower alkylcarbonyloxy group” refers to a group formed by replacingthe hydrogen atom of a hydroxy group with a lower alkylcarbonyl group.Specific examples thereof include methylcarbonyloxy, ethylcarbonyloxy,n-propylcarbonyloxy, n-butylcarbonyloxy, n-pentylcarbonyloxy,n-hexylcarbonyloxy, n-heptylcarbonyloxy, n-octylcarbonyloxy,isopropylcarbonyloxy, isobutylcarbonyloxy, sec-butylcarbonyloxy,tert-butylcarbonyloxy and isopentylcarbonyloxy groups and the like.

The “arylcarbonyloxy group” refers to a group formed by replacing thehydrogen atom of a hydroxy group with an arylcarbonyl group. Specificexamples thereof include phenylcarbonyloxy, naphthylcarbonyloxy,anthrylcarbonyloxy and phenanthrylcarbonyloxy groups and the like.

The “lower alkylene group” refers to a straight chain or branchedalkylene group having 1 to 8 carbon atoms, preferably 1 to 6, especiallypreferably 1 to 4. Specific examples thereof include methylene,ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene,heptamethylene, octamethylene, methylmethylene and ethylmethylene groupsand the like.

The “halogenated lower alkyl group” refers to a group formed byreplacing the hydrogen atom of a lower alkyl group with one or aplurality of halogen atoms. Specific examples thereof includedifluoromethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl,dichloromethyl, trichloromethyl, trichloroethyl, trichloropropyl and thelike.

The “halogenated lower alkoxy group” refers to a group formed byreplacing the hydrogen atom of a lower alkoxy group with one or aplurality of halogen atoms. Specific examples thereof includedifluoromethoxy, trifluoromethoxy, trifluoroethoxy, trifluoropropoxy,dichloromethoxy, trichloromethoxy, trichloroethoxy, trichloropropoxy andthe like.

The “lower alkyl group which may have a substituent”, “lower alkenylgroup which may have a substituent”, “lower alkynyl group which may havea substituent”, “lower alkoxy group which may have a substituent”,“lower alkenyloxy group which may have a substituent” and/or “loweralkynyloxy group which may have a substituent” refer to a “lower alkylgroup”, a “lower alkenyl group”, a “lower alkynyl group”, a “loweralkoxy group”, a “lower alkenyloxy group” and/or a “lower alkynyloxygroup” which may have one or a plurality of substituents selected fromthe following α¹ group, preferred one or a plurality of substituentsselected from the following α², respectively.

[α¹ Group]

A halogen atom, a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a hydroxy group, a lower alkoxy group, a halogenated lower alkoxygroup, a lower alkenyloxy group, a lower alkynyloxy group, a lowercycloalkyloxy group, an aryloxy group, a heterocyclic oxy group, amercapto group, a lower alkylthio group, a lower alkenylthio group, alower alkynylthio group, a lower cycloalkylthio group, an arylthiogroup, a heterocyclic thio group, a formyl group, a lower alkylcarbonylgroup, an arylcarbonyl group, a carboxy group, a lower alkoxycarbonylgroup, an aryloxycarbonyl group, a lower alkylcarbonyloxy group, anarylcarbonyloxy group, —NR^(a)R^(b), a nitro group and a cyano group.

[α² Group]

A halogen atom, a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a hydroxy group, a lower alkoxy group, a lower alkenyloxy group,a lower alkynyloxy group, a lower cycloalkyloxy group, an aryloxy group,a heterocyclic oxy group and —NR^(a)R^(b).

The “lower cycloalkyl group which may have a substituent”, “aryl groupwhich may have a substituent”, “heterocyclic group which may have asubstituent”, “lower cycloalkyloxy group which may have a substituent”,“aryloxy group which may have a substituent” and/or “heterocyclic oxygroup which may have a substituent” refer to a “lower cycloalkyl group”,an “aryl group”, a “heterocyclic group”, a “lower cycloalkyloxy group”,an “aryloxy group” and/or a “heterocyclic oxy group” which may have oneor a plurality of substituents selected from the following β group,respectively.

[β Group]

A halogen atom, a lower alkyl group, a halogenated lower alkyl group, alower alkenyl group, a lower alkynyl group, a lower cycloalkyl group, anaryl group, a heterocyclic group, a hydroxy group, a lower alkoxy group,a halogenated lower alkoxy group, a lower alkenyloxy group, a loweralkynyloxy group, a lower cycloalkyloxy group, an aryloxy group, aheterocyclic oxy group, a mercapto group, a lower alkylthio group, alower alkenylthio group, a lower alkynylthio group, a lowercycloalkylthio group, an arylthio group, a heterocyclic thio group, aformyl group, a lower alkylcarbonyl group, an arylcarbonyl group, acarboxy group, a lower alkoxycarbonyl group, an aryloxycarbonyl group, alower alkylcarbonyloxy group, an arylcarbonyloxy group, —NR^(a)R^(b), anitro group and a cyano group.

R^(a) and R^(b) in the above “—NR^(a)R^(b)” may be the same or differentand represent a substituent selected from the following γ¹ group,preferably the following γ² group.

[γ¹ Group]

A hydrogen atom, a lower alkyl group, a lower alkenyl group, a loweralkynyl group, a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a lower alkoxycarbonyl group and an aryloxycarbonyl group.

[γ² Group]

A hydrogen atom, a lower alkyl group, an aryl group, a heterocyclicgroup, a lower alkoxycarbonyl group and an aryloxycarbonyl group.

The term “a plurality of groups” as used in this invention means thateach group may be the same or different and stands for 2 or more but notmore than the number of groups which can be introduced intosubstitutable position(s), and the number is preferably 2 or 3, and 2 isparticularly preferable.

Further, in this invention, a hydrogen atom and a halogen atom are alsoincluded in the concept of the “group”.

The “glucocorticoid receptor modulator” as used herein refers to amodulator that exhibits a pharmaceutical action by binding toglucocorticoid receptor. Examples thereof include glucocorticoidreceptor agonists, glucocorticoid receptor antagonists and the like.

The “salt” of the present compound is not particularly limited as longas it is a pharmaceutically acceptable salt. Examples thereof includesalts with an inorganic acid such as hydrochloric acid, hydrobromicacid, hydroiodic acid, nitric acid, sulfuric acid or phosphoric acid ofthe like; salts with an organic acid such as acetic acid, fumaric acid,maleic acid, succinic acid, citric acid, tartaric acid, adipic acid,gluconic acid, glucoheptonic acid, glucuronic acid, terephthalic acid,methanesulfonic acid, lactic acid, hippuric acid, 1,2-ethanedisulfonicacid, isethionic acid, lactobionic acid, oleic acid, pamoic acid,polygalacturonic acid, stearic acid, tannic acid,trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonicacid, lauryl sulfate ester, methyl sulfate, naphthalenesulfonic acid,sulfosalicylic acid or the like; quaternary ammonium salts with methylbromide, methyl iodide or the like; salts with a halogen ion such as abromine ion, a chlorine ion, an iodine ion or the like; salts with analkali metal such as lithium, sodium, potassium or the like; salts withan alkaline earth metal such as calcium, magnesium or the like; saltswith a metal such as iron, zinc or the like; salts with ammonia; saltswith an organic amine such as triethylenediamine, 2-aminoethanol,2,2-iminobis(ethanol), 1-deoxy-1-(methylamino)-2-D-sorbitol,2-amino-2-(hydroxymethyl)-1,3-propanediol, procaine,N,N-bis(phenylmethyl)-1,2-ethanediamine or the like.

In the case where there are geometrical isomers and/or optical isomersin the present compound, these isomers are also included in the scope ofthe present invention.

In the case where there are proton tautomers in the present compound,these tautomers (keto-form, enol-form) are also included in the scope ofthe present invention.

In the case where there are hydrate and/or solvate in the presentcompound, these hydrate and/or solvate are also included in the scope ofthe present invention.

In the case where there are polymorphism and polymorphism group(polymorphism system) in the present compound, these polymorphism andpolymorphism group (polymorphism system) are also included in the scopeof the present invention. “Polymorphism group (polymorphism system)”herein means each crystal form in each step where the crystal formchanges depending on condition and states (the states also include astate of drug formulation) of manufacture, crystallization andpreservation and the like, and the entire process.

(a) Preferred examples of the present compound include compounds inwhich the respective groups are groups as defined below and saltsthereof in the compounds represented by the general formula (1) andsalts thereof.

(a1) R¹ represents a hydrogen atom or a lower alkyl group; and/or

(a2) R² represents a hydrogen atom or a lower alkyl group; and/or

(a3) R³ and R⁴ may be the same or different and represent a hydrogenatom or a lower alkyl group; and/or

(a4) R⁵ represents a hydrogen atom or a lower alkyl group; and/or

(a5) R⁶ represents a halogen atom, a lower alkyl group, a hydroxy group,a lower alkoxy group, a nitro group or a cyano group; and/or

(a6) X represents —CO—, —C(O)NR⁸—, —S(O)— or —S(O)₂—; and/or

(a7) R⁷ and/or R⁸ may be the same or different and represent a hydrogenatom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group,a lower cycloalkyl group, an aryl group, a heterocyclic group, a loweralkoxy group, a lower alkenyloxy group, a lower alkynyloxy group, alower cycloalkyloxy group, an aryloxy group or a heterocyclic oxy group;

in the case where R⁷ and/or R⁸ is a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower alkoxy group, a lower alkenyloxygroup or a lower alkynyloxy group, the lower alkyl group, lower alkenylgroup, lower alkynyl group, lower alkoxy group, lower alkenyloxy groupor lower alkynyloxy group may have one or a plurality of groups selectedfrom a halogen atom, a lower cycloalkyl group, an aryl group, aheterocyclic group, a hydroxy group, a lower alkoxy group, a loweralkenyloxy group, a lower alkynyloxy group, a lower cycloalkyloxy group,an aryloxy group, a heterocyclic oxy group and —NR^(a)R^(b) assubstituent(s);

in the case where R⁷ and/or R⁸ is a lower cycloalkyl group, an arylgroup, a heterocyclic group, a lower cycloalkyloxy group, an aryloxygroup or a heterocyclic oxy group, the lower cycloalkyl group, arylgroup, heterocyclic group, lower cycloalkyloxy group, aryloxy group orheterocyclic oxy group may have one or a plurality of groups selectedfrom a halogen atom, a lower alkyl group, a halogenated lower alkylgroup, an aryl group, a lower alkenyl group, a lower alkynyl group, alower cycloalkyl group, an aryl group, a heterocyclic group, a hydroxygroup, a lower alkoxy group, a halogenated lower alkoxy group, a loweralkenyloxy group, a lower alkynyloxy group, a lower cycloalkyloxy group,an aryloxy group, a heterocyclic oxy group, a mercapto group, a loweralkylthio group, a lower alkenylthio group, a lower alkynylthio group, alower cycloalkylthio group, an arylthio group, a heterocyclic thiogroup, a lower alkylcarbonyl group, an arylcarbonyl group, a loweralkoxycarbonyl group, an aryloxycarbonyl group, a lower alkylcarbonyloxygroup, an arylcarbonyloxy group, —NR^(a)R^(b), a nitro group and a cyanogroup as substituent(s);

R^(a) and R^(b) may be the same or different and represent a hydrogenatom, a lower alkyl group, a lower alkenyl group, a lower alkynyl group,a lower cycloalkyl group, an aryl group, a heterocyclic group, a loweralkoxycarbonyl group or an aryloxycarbonyl group; and/or

(a8) Y represents a lower alkylene group; and/or

(a9) p represents 0, 1, 2 or 3, in the case where p is 2 or 3, each R⁶may be the same or different.

That is, in the compounds represented by the general formula (1) andsalts thereof, preferred examples include compounds that comprise one ora combination of two or more selected from the above (a1), (a2), (a3),(a4), (a5), (a6), (a7), (a8) and (a9), and salts thereof.

(b) More preferred examples of the present compound include compounds inwhich the respective groups are groups as defined below and saltsthereof in the compounds represented by the general formula (1) andsalts thereof.

(b1) R¹ represents a hydrogen atom or a lower alkyl group; and/or

(b2) R² represents a hydrogen atom or a lower alkyl group; and/or

(b3) R³ and R⁴ may be the same or different and represent a hydrogenatom or a lower alkyl group; and/or

(b4) R⁵ represents a hydrogen atom or a lower alkyl group; and/or

(b5) R⁶ represents a halogen atom, a lower alkyl group, a hydroxy groupor a lower alkoxy group; and/or

(b6) X represents —CO—, —C(O)NR⁸—, —S(O)— or —S(O)₂—; and/or

(b7) R⁷ and/or R⁸ may be the same or different and represent a hydrogenatom, a lower alkyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower alkoxy group, a lower cycloalkyloxy group,an aryloxy group or a heterocyclic oxy group;

in the case where R⁷ and/or R⁸ is a lower alkyl group, the lower alkylgroup may have one or a plurality of groups selected from a halogen atomand —NR^(a)R^(b) as substituent(s);

in the case where R⁷ and/or R⁸ is a lower cycloalkyl group, an arylgroup, a heterocyclic group, a lower cycloalkyloxy group, an aryloxygroup or a heterocyclic oxy group, the lower cycloalkyl group, arylgroup, heterocyclic group, lower cycloalkyloxy group, aryloxy group orheterocyclic oxy group may have one or a plurality of groups selectedfrom a halogen atom, a lower alkyl group, a hydroxy group, a loweralkoxy group, a mercapto group, a lower alkylthio group, a loweralkylcarbonyl group, a lower alkoxycarbonyl group, a loweralkylcarbonyloxy group and a nitro group as substituent(s);

R^(a) and R^(b) may be the same or different and represent a hydrogenatom or a lower alkyl group; and/or

(b8) Y represents a lower alkylene group; and/or

(b9) p represents 0, 1, 2 or 3, in the case where p is 2 or 3, each R⁶may be the same or different.

That is, in the compounds represented by the general formula (1) andsalts thereof, more preferred examples include compounds that compriseone or a combination of two or more selected from the above (b1), (b2),(b3), (b4), (b5), (b6), (b7), (b8) and (b9), and salts thereof.

(c) Further more preferred examples of the present compound includecompounds in which the respective groups are groups as defined below andsalts thereof in the compounds represented by the general formula (1)and salts thereof.

(c1) R¹ represents a lower alkyl group; and/or

(c2) R² represents a hydrogen atom; and/or

(c3) R³ and R⁴ represent a lower alkyl group; and/or

(c4) R⁵ represents a lower alkyl group; and/or

(c5) R⁶ represents a halogen atom, a lower alkyl group or a lower alkoxygroup; and/or

(c6) X represents —CO—, —C(O)NR⁸— or —S(O)₂—; and/or

(c7) R⁷ represents a lower alkyl group, a lower cycloalkyl group, anaryl group, a heterocyclic group, a lower alkoxy group or an aryloxygroup;

in the case where R⁷ is a lower alkyl group, the lower alkyl group mayhave one or a plurality of groups selected from a halogen atom and—NR^(a)R^(b) as substituent(s);

in the case where R⁷ is an aryl group, a heterocyclic group or anaryloxy group, the aryl group, heterocyclic group or aryloxy group mayhave one or a plurality of groups selected from a halogen atom, a loweralkyl group, a lower alkoxy group, a lower alkylthio group, a loweralkylcarbonyl group, a lower alkoxycarbonyl group, a loweralkylcarbonyloxy group and a nitro group as substituent(s);

R^(a) and R^(b) may be the same or different and represent a hydrogenatom or a lower alkyl group; and/or

(c8) R⁸ represents a hydrogen atom or a lower alkyl group; and/or

(c9) Y represents a lower alkylene group; and/or

(c10) p represents 0, 1 or 2, in the case where p is 2, each R⁶ may bethe same or different.

That is, in the compounds represented by the general formula (1) andsalts thereof, further more preferred examples include compounds thatcomprise one or a combination of two or more selected from the above(c1), (c2), (c3), (c4), (c5), (c6), (c7), (c8), (c9) and (c10), andsalts thereof.

(d) Further more preferred examples of the present compound includecompounds in which the respective groups are groups as defined below andsalts thereof in the compounds represented by the general formula (1)and salts thereof.

(d1) R¹ represents a lower alkyl group; and/or

(d2) R² represents a hydrogen atom; and/or

(d3) R³ and R⁴ represent a lower alkyl group; and/or

(d4) R⁵ represents a lower alkyl group; and/or

(d5) R⁶ represents a halogen atom, a lower alkyl group or a lower alkoxygroup; and/or

(d6) X represents —CO—, —C(O)NR⁸— or —S(O)₂—; and/or

(d7) R⁷ represents a lower alkyl group, a lower cycloalkyl group, anaryl group, a heterocyclic group, a lower alkoxy group or an aryloxygroup;

in the case where R⁷ is a lower alkyl group, the lower alkyl group mayhave one or a plurality of groups selected from a halogen atom and—NR^(a)R^(b) as substituent(s);

in the case where R⁷ is an aryl group, the aryl group may have one or aplurality of groups selected from a halogen atom, a lower alkyl group, alower alkoxy group, a lower alkylthio group, a lower alkylcarbonylgroup, a lower alkoxycarbonyl group, a lower alkylcarbonyloxy group anda nitro group as substituent(s);

in the case where R⁷ is a heterocyclic group, the heterocyclic group mayhave one or a plurality of groups selected from a halogen atom, a loweralkyl group and a lower alkoxy group as substituent(s);

in the case where R⁷ is an aryloxy group, the aryloxy group may have oneor a plurality of halogen atoms as substituent(s);

R^(a) and R^(b) may be the same or different and represent a hydrogenatom or a lower alkyl group; and/or

(d8) R⁸ represents a hydrogen atom or a lower alkyl group; and/or

(d9) Y represents a lower alkylene group; and/or

(d10) p represents 0, 1 or 2, in the case where p is 2, each R⁶ may bethe same or different.

That is, in the compounds represented by the general formula (1) andsalts thereof, further more preferred examples include compounds thatcomprise one or a combination of two or more selected from the above(d1), (d2), (d3), (d4), (d5), (d6), (d7), (d8), (d9) and (d10), andsalts thereof.

(e) Specific examples of the present compound represented by thepreferred substituent(s) include compounds in which R¹, R³, R⁴ and R⁵represents a methyl group, R² represents a hydrogen atom, Y is amethylene group in the general formula (1) and satisfy the aboveconditions (a), (b), (c) and/or (d), and salts thereof.

(f) Particularly preferred specific examples of the present compoundinclude the following compounds and salts thereof.

-   6-[4-(Furan-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-(4-Benzoyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(2-methoxybenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-(Furan-3-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiophen-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-(4-Isopropylcarbonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiophen-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(furan-2-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(4-methoxybenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-(4-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(2-methylthiobenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline-   6-[4-(3-Acetylbenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-(3-Chlorothiophen-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiazol-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(6-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(furan-3-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(2-methylthio    benzoyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-(4-Dimethylaminocarbonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[2-Methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(2-Methoxyphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-(4-Isopropylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-(2-Methoxy-4-methylsulfonyloxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-(4-Cyclopropylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxy    phenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-(4-Cyclopentylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(5-Fluoro-2-methylphenylaminomethyl)-6-(2-methoxy-4-methylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   6-[4-[N-(2-Dimethylaminoethyl)-N-methylaminocarbonyloxy]-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,-   5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylaminocarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,    and-   6-[4-[N-(2-Dimethylaminoethyl)-N-methylaminocarbonyloxy]-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline.

The present compound can be synthesized according to the followingprocedures. The individual concrete preparation procedures are explainedin details in the section of “Production Examples” in Examples. Theseexamples are intended to make the present invention more clearlyunderstandable, and do not limit the scope of the present invention. Thehal shown in the following synthetic routes represents a halogen atom.The fmoc represents a 9-fluorenylmethoxycarbonyl group.

The present compound (I)-(a) (the compound in which Y is a methylenegroup, R² is H, R³, R⁴ and R⁵ are methyl groups, X is C(O) in thegeneral formula (1)) can be synthesized according to the syntheticroute 1. Namely, the compound (I)-(a) can be given by the reaction ofthe compound (II) with a corresponding halide (III) in an organicsolvent such as methylene dichloride, N,N-dimethylformamide (hereinafterreferred to as DMF) in the presence of a base such as triethylamine,diisopropylethylamine (hereinafter referred to as DIEA) at 0° C. to roomtemperature for 1 hour to 2 days.

And the compound (I)-(a) can be given by the reaction of the compound(II) with a corresponding carboxylic acid (IV) in an organic solventsuch as methylene dichloride, DMF in the presence of a base such astriethylamine, DIEA and a condensation agent such asN,N′-dicyclohexylcarbodiimide,O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate at 0° C. to room temperature for 30 minutes to 3days.

The present compound (I)-(b) (the compound in which Y is a methylenegroup, R² is H, R³, R⁴ and R⁵ are methyl groups, X is S(O)₂ in thegeneral formula (1)) can be synthesized according to the synthetic route2. Namely, the compound (I)-(b) can be given by the reaction of thecompound (II) with a corresponding halide (V) in an organic solvent suchas methylene dichloride, DMF in the presence of a base such astriethylamine, DIEA at 0° C. to room temperature for 1 hour to 2 days.

The present compound (I)-(c) (the compound in which Y is a methylenegroup, R² is H, R³, R⁴ and R⁵ are methyl groups, X is C(O)NR⁸ and R⁸ isa hydrogen atom in the general formula (1)) can be synthesized accordingto the synthetic route 3. Namely, the compound (I)-(c) can be given bythe reaction of the compound (II) with a corresponding isocyanate (VI)in an organic solvent such as methylene dichloride, DMF in the presenceof a base such as triethylamine, DIEA at 0° C. to room temperature for30 minutes to 1 day.

The present compound (I)-(d) (the compound in which Y is a methylenegroup, R² is H, R³, R⁴ and R⁵ are methyl groups, X is C(O)NR⁸ in thegeneral formula (1)) can be synthesized according to the synthetic route4. Namely, the compound (I)-(d) can be given by the reaction of thecompound (II) with 1,1′-carbonyldiimidazole in an organic solvent suchas methylene dichloride, tetrahydrofuran (hereinafter referred to asTHF) at room temperature to 50° C. for 30 minutes to 12 hours followedby the reaction with a corresponding amine (VII) at room temperature to50° C. for 30 minutes to 5 hours.

The present compounds (I)-(a), (I)-(b), (I)-(c), and (I)-(d) can be alsosynthesized according to the synthetic route 5. Namely, the compound(I)-(a), (I)-(b), (I)-(c), and (I)-(d) can be given by the reaction ofthe compound (VIII) with a halide(III), a carboxylic acid (IV), a halide(V), an isocyanate (VI) or an amine (VII) according to synthetic route1, 2, 3 or 4 followed by the treatment with a base such as piperidine inan organic solvent such as DMF, methylene dichloride at 0° C. to 50° C.for 5 minutes to 24 hours.

The compound (II) and (VIII) can be synthesized according to thesynthetic route 6. Namely, the compound (X) can be given by the reactionof the compound (IX) with methanesulfonyl chloride in an organic solventsuch as methylene dichloride, DMF in the presence of a base such astriethylamine, DIEA at 0° C. to room temperature for 30 minutes to 3days. The compound (XII) can be given by the reaction of the compound(X) with a corresponding amine (XI) in an organic solvent such as DMF,methylene dichloride in the presence of a base such as potassiumcarbonate, DIEA, sodium hydride at 50° C. to 100° C. for 1 hour to 2days. The compound (II) can be given by the treatment of the compound(XII) in an organic solvent such as methylene dichloride, 1,4-dioxane inthe presence of an acid such as hydrogen chloride, trifluoroacetic acid.The compound (VIII) can be given by the reaction of the compound (II)with 9-fluorenylmethoxycarbonyl chloride in a solvent such as1,4-dioxane, water in the presence of a base such as sodium hydrogencarbonate at 0° C. to 50° C. for 1 hour to 24 hours.

The compound (IX) can be synthesized according to the synthetic route 7.Namely, the compound (XV) can be given by the reaction of a boronic acid(XIII) with a halide or triflate (XIV) in a solvent such as DMF,ethanol, toluene, water in the presence of a base such as cesiumcarbonate, sodium carbonate, potassium phosphate and a catalyst such asbis(triphenylphosphine)palladium (II) dichloride,tetrakis(triphenylphosphine)palladium (0) at 50° C. to 120° C. for 12hours to 2 days. The compound (XVI) can be given by the treatment of theobtained compound (XV) in a solvent such as methylene dichloride, THF inthe presence of an acid such as boron tribromide, hydrogen chloride at−78° C. to room temperature for 1 hour to 1 day. The compound (XVII) canbe given by the treatment of the obtained compound (XVI) under hydrogenatmosphere in an organic solvent such as methanol, ethanol, 1,4-dioxane,THF in the presence of a catalyst such as palladium carbon, platinumdioxide at room temperature for 2 hours to 2 days. The compound (XVIII)can be given by the treatment of the obtained compound (XVII) in acetonein the presence of iodine at 80° C. to 130° C. for 24 hours to 5 days.The compound (XIX) can be given by the reaction of the obtained compound(XVIII) with chlorodimethylether in an organic solvent such as methylenedichloride, DMF in the presence of a base such as potassium carbonate,triethylamine, DIEA. The compound (XX) can be given by the treatment ofthe obtained compound (XIX) in an organic solvent such as diethyl ether,THF in the presence of a reducing agent such as lithium aluminiumhydride at 0° C. to 50° C. for 1 hour to 1 day. The compound (VIII) canbe given by the reaction of the compound (XX) with a correspondinghalide (XXI) in an organic solvent such as DMF, ethanol in the presenceof a base such as potassium carbonate, DIEA at room temperature to 100°C. for 1 hour to 24 hours.

A detailed explanation of this matter will be described in the sectionof “Pharmacological Test” in Examples described below. In order to findthe usefulness of the present compound as a pharmaceutical, aglucocorticoid receptor competitor assay was carried out by afluorescence polarization method by using a glucocorticoid receptorcompetitor assay kit (manufactured by Invitrogen, cat No. P2816) tostudy the glucocorticoid receptor binding activity of the presentcompound. As a result, the present compound showed an excellentglucocorticoid receptor binding activity to the glucocorticoid receptor.

Incidentally, the glucocorticoid receptor is associated with theoccurrence of various diseases as described above, therefore, thepresent compound having an excellent binding activity to theglucocorticoid receptor is useful as a glucocorticoid receptormodulator.

The present compound can be administered either orally or parenterally.Examples of the dosage form include a tablet, a capsule, a granule, apowder, an injection, an eye drop, a suppository, percutaneousabsorption preparation, an ointment, an aerosol (including an inhalant)and the like and such a preparation can be prepared using a commonlyused technique.

For example, an oral preparation such as a tablet, a capsule, a granuleor a powder can be prepared by optionally adding a necessary amount ofan excipient such as lactose, mannitol, starch, crystalline cellulose,light silicic anhydride, calcium carbonate or calcium hydrogenphosphate; a lubricant such as stearic acid, magnesium stearate or talc;a binder such as starch, hydroxypropyl cellulose, hydroxypropylmethylcellulose or polyvinylpyrrolidone; a disintegrant such as carboxymethylcellulose, low-substituted hydroxypropylmethyl cellulose or calciumcitrate; a coating agent such as hydroxypropylmethyl cellulose, macrogolor a silicone resin; a stabilizer such as ethyl p-hydroxybenzoate orbenzyl alcohol; a corrigent such as a sweetener, a sour agent or aflavor, or the like.

A parenteral preparation such as an injection or an eye drop can beprepared by optionally adding a necessary amount of a tonicity agentsuch as sodium chloride, concentrated glycerin, propylene glycol,polyethylene glycol, potassium chloride, sorbitol or mannitol; a buffersuch as sodium phosphate, sodium hydrogen phosphate, sodium acetate,citric acid, glacial acetic acid or trometamol; a surfactant such aspolysorbate 80, polyoxy 40 stearate or polyoxyethylene hydrogenatedcastor oil 60; a stabilizer such as sodium citrate or sodium edetate; apreservative such as benzalkonium chloride, paraben, benzothoniumchloride, p-hydroxybenzoate ester, sodium benzoate or chlorobutanol; apH adjusting agent such as hydrochloric acid, citric acid, phosphoricacid, glacial acetic acid, sodium hydroxide, sodium carbonate or sodiumhydrogen carbonate; a soothing agent such as benzyl alcohol, or thelike.

This invention also provides a preventive or therapeutic method forglucocorticoid receptor related diseases, for examples, metabolicdisorders such as diabetes and obesity, inflammatory diseases such asenteritis and chronic obstructive pulmonary diseases, autoimmunediseases such as connective tissue diseases, allergic diseases such asasthma, atopic dermatitis and allergic rhinitis, central nervous systemdiseases such as psychiatric disorders, Alzheimer's disease and drug usedisorders, cardiovascular diseases such as hypertension, hypercalcemia,hyperinsulinemia and hyperlipidemia, homeostasis-related diseasescausing an abnormality of neuro-immune-endocrine balance, glaucoma andthe like.

The dose of the present compound can be appropriately selected dependingon the kinds of the diseases, symptoms, age, dosage form or the like.For example, in the case of an oral preparation, it can be administeredin an amount of generally 0.01 to 1000 mg, preferably 1 to 100 mg perday in a single dose or several divided doses. Further, in the case ofan eye drop, a preparation containing the present compound at aconcentration of generally 0.0001% to 10% (w/v), preferably 0.01% to 5%(w/v) can be administered in a single dose or several divided doses.

Hereinafter, Production Examples of the present compound, PreparationExamples and results of Pharmacological Test will be described. However,these examples are described for the purpose of understanding thepresent invention better and are not meant to limit the scope of thepresent invention.

PRODUCTION EXAMPLES Reference Example 15-Hydroxymethyl-6-(2-methoxy-4-methoxymethoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 1) Methyl2-(2,4-dimethoxyphenyl)-5-nitrobenzoate (Reference Compound No. 1-(1))

A mixture of 2,4-dimethoxyphenylboronic acid (25.0 g, 137 mmol), methyl2-bromo-5-nitrobenzoate (35.7 g, 137 mmol), cesium carbonate (89.4 g,274 mmol) and bis(triphenylphosphine)palladium (II) dichloride (4.81 g,6.85 mmol) was suspended in N,N-dimethylformamide (450 mL), and then thesuspension was stirred under argon atmosphere at 80° C. overnight. Aftercooling down, ethyl acetate (200 mL), diethylether (400 mL) and water(1000 mL) were added thereto and the mixture was separated into a waterphase and an organic layer. The water layer was extracted with a mixedsolvent of ethyl acetate (150 mL)-diethylether (150 mL) (twice). Thecombined organic layer was washed with water (500 mL, 3 times) andsaturated brine (500 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure to givethe titled reference compound as a brown oil. (Quantitative)

¹H-NMR (400 MHz, CDCl₃) δ 3.71 (s, 3H), 3.76 (s, 3H), 3.87 (s, 3H), 6.49(d, J = 2.3 Hz, 1H), 6.60 (dd, J = 8.3, 2.3 Hz, 1H), 7.20 (d, J = 8.3Hz, 1H), 7.49 (d, J = 8.5 Hz, 1H), 8.35 (dd, J = 8.5, 2.5 Hz, 1H), 8.67(d, J = 2.5 Hz, 1H)

3-Hydroxy-8-nitrobenzo[c]chromen-6-one (Reference Compound No. 1-(2))

A solution of methyl 2-(2,4-dimethoxyphenyl)-5-nitrobenzoate (ReferenceCompound No. 1-(1), 43.5 g, 137 mmol) in anhydrous methylene dichloride(250 mL) was cooled to −78° C., boron tribromide (96.2 g, 384 mmol) wasadded thereto, and then the mixture was stirred at room temperature for1 hour. The mixture was cooled to −50° C. and methanol (300 mL) wasadded thereto. The resulting precipitates were filtered off withmethanol to give the titled reference compound (18.0 g) as a yellowsolid. (Yield 51%)

¹H-NMR (400 MHZ, DMSO-d₆) δ 6.81 (d, J = 2.4 Hz, 1H), 6.91 (dd, J = 8.8,2.4 Hz, 1H), 8.28 (d, J = 8.8 Hz, 1H), 8.50 (d, J = 8.9 Hz, 1H), 8.60(dd, J = 8.9, 2.4 Hz, 1H), 8.82 (d, J = 2.4 Hz, 1H), 10.75 (s, 1H)

8-Amino-3-hydroxybenzo[c]chromen-6-one (Reference Compound No. 1-(3))

3-Hydroxy-8-nitrobenzo[c]chromen-6-one (Reference Compound No. 1-(2),52.01 g, 202 mmol) was dissolved in methanol (150mL)-N,N-dimethylformamide (600 mL), 10% palladium on charcoal (5.00 g)was added thereto, and then the reaction mixture was stirred underhydrogen atmosphere (3 kgf/cm²) at room temperature overnight. After theunsoluble materials were filtered out, the methanol was removed underreduced pressure. Water (2 L) was added to the residue. The precipitatedsolid was filtered off and dried at 90° C. under reduced pressure togive the titled reference compound (44.02 g) as a pale yellow solid.(Yield 96%)

¹H-NMR (400 MHz, DMSO-d₆) δ 6.02(s, 2 H), 7.17(dd, J = 8.5, 2.4 Hz, 1H), 7.37-7.41(m, 1 H), 7.37 (d, J = 2.4 Hz, 1 H), 7.96 (ddd, J = 9.3,5.4, 2.2 Hz, 1 H), 8.08(d, J = 8.5, Hz, 1 H)

8-Hydroxy-2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one(Reference Compound No. 1-(4))

In a pressure tube, 8-amino-3-hydroxybenzo[c]chromen-6-one (ReferenceCompound No. 1-(3), 40.0 g, 176 mmol) was dissolved in acetone (440mL)-N-methylpyrrolidone (240 mL), iodine (17.9 g, 70.5 mmol) was addedthereto, the pressure tube was sealed, and then the reaction mixture wasstirred at 110° C. for 3 days. After cooling down, acetone was removedunder reduced pressure. To the obtained residue, ethyl acetate (700 mL),hexane (150 mL) and 1% aqueous sodium thiosulfate solution (700 mL) wereadded thereto and the mixture was separated into a water phase and anorganic layer. The water layer was extracted with a mixed solvent ofethyl acetate (250 mL)-hexane (50 mL) (3 times). The combined organiclayer was washed with water (500 mL, 3 times) and saturated brine (500mL) successively, dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. To the obtained residue,chloroform (150 mL) was added and the unsoluble materials were filteredout. After the filtrate was concentrated, the residue was purified bysilica gel column chromatography (hexane-ethyl acetate) to give thetitled reference compound (26.0 g) as a yellow solid. (Yield 48%)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.23(s, 6 H), 1.97(s, 3 H), 5.48(s, 1 H),7.05 (s, 1 H), 7.19(d, J = 8.9 Hz, 1 H), 7.37(td, J = 9.7, 7.6 Hz, 1 H),7.95 (ddd, J = 9.7, 5.2, 1.8 Hz, 1 H), 7.98(d, J = 8.9, Hz, 1 H)

8-Methoxymethoxy-2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one(Reference Compound No. 1-(5))

A mixture of8-hydroxy-2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one(Reference Compound No. 1-(4), 1.00 g, 3.25 mmol), chlorodimethylether(420 μL, 5.53 mmol) and potassium carbonate (1.35 g, 9.77 mmol) wassuspended in anhydrous N,N-dimethylformamide (15 mL) and the suspensionwas stirred at 50° C. overnight. After cooling down, ethyl acetate (100mL) and diethylether (100 mL) were added thereto. The whole was washedwith water (150 mL, 100 mL) and saturated brine (100 mL) successively,dried over anhydrous magnesium sulfate, and then the solvent was removedunder reduced pressure. The obtained residue was purified by silica gelcolumn chromatography (hexane-ethyl acetate) to give the titledreference compound (747 mg) as a yellow solid. (Yield 66%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.22(s, 6 H), 1.95(s, 3 H), 3.40(s, 3 H),5.27 (s, 2 H), 5.43(s, 1 H), 6.85(s, 1 H), 6.98(d, J = 9.3 Hz, 1 H),6.99(s, 1 H), 7.16(d, J = 8.8 Hz, 1 H), 7.92(d, J = 8.8 Hz, 1 H),8.04(d, J = 9.3 Hz, 1 H)

6-(2-Hydroxy-4-methoxymethoxyphenyl)-5-hydroxymethyl-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 1-(6))

Lithium aluminum hydride (167 mg, 4.40 mmol) was suspended in anhydroustetrahydrofuran (3 mL). A solution of8-methoxymethoxy-2,2,4-trimethyl-1,2-dihydro-6-oxa-1-azachrysen-5-one(Reference Compound No. 1-(5), 744.1 mg, 2.12 mmol) in anhydroustetrahydrofuran (10 mL) was added dropwise to the suspension at 0° C.,the reaction mixture was stirred at the same temperature for 30 minutes.Ethyl acetate (2 mL) and water (1 mL) were added to the reaction mixturesuccessively, and then ethyl acetate (150 mL) was added thereto. 1Naqueous HCl solution (6 mL) was added, the mixture was washed with water(100 mL, twice) and saturated brine (50 mL) successively, and then driedover anhydrous magnesium sulfate. The solvent was removed under reducedpressure to give the titled reference compound (750.6 mg) as a paleyellow amorphous product. (Quantitative)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.13(s, 3 H), 1.20(s, 3 H), 2.23(s, 3 H),3.39 (s, 3 H), 4.26(dd, J = 11.0, 6.6 Hz, 1 H), 4.33 (t, J = 6.6 Hz, 1H), 4.44 (dd, J = 11.0, 6.6 Hz, 1 H), 5.14(s, 2 H), 5.33 (s, 1 H),5.76(s, 1 H), 6.49(dd, J = 8.4, 2.6 Hz, 1 H), 6.53(d, J = 8.3 Hz, 1 H),6.56(d, J = 2.6 Hz, 1 H), 6.65(d, J = 8.3 Hz, 1 H), 6.97(d, J = 8.4 Hz,1 H), 9.23(s, 1 H)

5-Hydroxymethyl-6-(2-methoxy-4-methoxymethoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 1)

A mixture of6-(2-hydroxy-4-methoxymethoxyphenyl)-5-hydroxymethyl-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 1-(6), 746.1 mg, 2.10 mmol), methyl iodide (131μL, 2.10 mmol) and potassium carbonate (582 mg, 4.21 mmol) was suspendedin anhydrous N,N-dimethylformamide (10 mL) and the suspension wasstirred at 50° C. for 1 hour. After cooling down, the mixture wasdiluted with ethyl acetate (50 mL) and diethylether (50 mL). The mixturewas washed with water (100 mL, twice) and saturated brine (50 mL)successively, dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl acetate) togive the titled reference compound (513.2 mg) as a colorless solid.(Yield 66%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.13(s, 3 H), 1.20(s, 3 H), 2.23(s, 3 H),3.41 (s, 3 H), 3.65(s, 3 H), 4.14(d, J = 12.2 Hz, 1 H), 4.33(br s, 1 H),4.45(d, J = 12.2 Hz, 1 H), 5.22(s, 2 H), 5.32 (s, 1 H), 5.78(s, 1 H),6.51(d, J = 8.3 Hz, 1 H), 6.61-6.64(m, 2 H), 6.66 (d, J = 2.4 Hz, 1 H),7.05 (d, J = 8.3 Hz, 1 H)

Reference Example 25-Chloromethyl-6-(2-methoxy-4-methoxymethoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 2)

5-Hydroxymethyl-6-(2-methoxy-4-methoxymethoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 1, 1.02 g, mmol) was dissolved in anhydrousmethylene dichloride (10 mL), and then triethylamine (0.490 mL, 3.52mmol) and methanesulfonyl chloride (231 L, mmol) were addedsuccessively. The reaction mixture was stirred at room temperature for 5hours. Chloroform (50 mL) and water (50 mL) were added to the reactionmixture and separated. The organic layer was washed with saturated brine(50 mL), dried over anhydrous magnesium sulfate, and then the solventwas removed under reduced pressure. The obtained residue was purified bysilica gel column chromatography (hexane-ethyl acetate) to give thetitled reference compound (515 mg) as an orange amorphous product.(Yield 49%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.14(s, 3 H), 1.20(s, 3 H), 2.26(s, 3 H),3.42 (s, 3 H), 3.67(s, 3 H), 4.40(d, J = 11.7 Hz, Hz, 1 H), 5.23(s, 2H), 5.45(s, 1 H), 6.01(br s, 1 H), 6.60(d, J = 8.2 Hz, 1 H0, 6.66(dd, J= 8.3, 2.4 Hz, 1 H), 6.66(d, J = 8.2 Hz, 1 H), 6.70(d, J = 2.4 Hz, 1 H),7.03(d, J = 8.3 Hz, 1 H)

Reference Example 36-(2-Methoxy-4-methoxymethoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline (Reference CompoundNo. 3-1)

A mixture of5-chloromethyl-6-(2-methoxy-4-methoxymethoxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 2, 262 mg, 0.675 mmol), 2-methoxyaniline (84 μL,0.74 mmol) and potassium carbonate (151 mg, 1.09 mmol) was suspended inanhydrous N,N-dimethylformamide (4 mL) and the suspension was stirred at80° C. overnight. After cooling down, ethyl acetate (20 mL) and water(20 mL) were added to the reaction mixture and separated. The organiclayer was washed with saturated brine (20 mL), dried over anhydrousmagnesium sulfate, and then the solvent was removed under reducedpressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (196 mg) as a yellow amorphous product. (Yield 61%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.14(s, 3 H), 1.21(s, 3 H), 2.06(s, 3 H),3.37 (s, 3 H), 3.64(s, 3 H), 3.71(s, 3 H), 3.84(dd, J = 12.1, 3.3 Hz, 1H), 4.03 (dd, J = 12.1, 6.5 Hz, 1 H), 4.23(dd, J = 6.5, 3.3 Hz, 1 H),5.17(s, 2 H), 5.38(s, 1 H), 5.95 (s, 1 H), 6.36(dd, J = 7.8, 1.4 Hz, 1H), 6.50 (td, J = 7.8, 1.4 Hz, 1 H), 6.58(dd, J = 8.3, 1.9 Hz, 1 H),6.58(d, J = 8.2 Hz, 1 H), 6.61(d, J = 1.9 Hz, 1 H), 6.67(td, J = 7.8,1.2 Hz, 1 H), 6.67 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.8, 1.2 Hz, 1H), 6.98(d, J = 8.3 Hz, 1 H)Using Reference Compound No. 2, the following Reference Compound (No.3-2) was obtained by a method similar to that of Reference Compound No.3-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.09(s, 3 H), 1.19(s, 3 H), 1.89(s, 3 H),2.03 (s, 3 H), 3.38(s, 3 H), 3.69(s, 3 H), 3.93(dd, J = 13.2, 5.0 Hz, 1H), 4.06(dd, J = 13.2, 4.3 Hz, 1 H), 4.17-4.19(m, 1 H), 5.19(s, 2 H),5.39 (s, 1 H), 5.96(s, 1 H), 6.05(dd, J = 12.2, 2.6 Hz, 1 H), 6.20(td, J= 8.5, 2.6 Hz, 1 H), 6.59 (d, J = 8.3 Hz, 1 H), 6.61(dd, J = 8.5, 2.6Hz, 1 H), 6.67(d, J = 2.6 Hz, 1 H), 6.70(d, J = 8.3 Hz, 1 H), 6.85-6.89(m ,1 H), 7.07(d, J = 8.5 Hz, 1 H)

Reference Example 46-(4-Hydroxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline (Reference Compound No.4-1)

6-(2-Methoxy-4-methoxymethoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 3-1, 181 mg, 0.381 mmol) was dissolved in1,4-dioxane (3 mL), 4N HCl/1,4-dioxane solution (1 mL) was addedthereto, and then the mixture was stirred at room temperature for 2.5hours. The mixture was diluted with ethyl acetate (30 mL), washed withsaturated aqueous sodium hydrogen carbonate solution (30 mL), water (30mL) and saturated brine (30 mL) successively, dried over anhydrousmagnesium sulfate, and then the solvent was removed under reducedpressure. The obtained residue was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled referencecompound (101 mg) as a pale orange solid. (Yield 62%)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.13(s, 3 H), 1.21(s, 3 H), 2.06(s, 3 H),3.59 (s, 3 H), 3.71(s, 3 H), 3.83(dd, J = 12.2, 3.4 Hz, 1 H), 4.02(dd, J= 12.2, 6.7 Hz, 1 H), 4.23 (dd, J = 6.7, 3.4 Hz, 1 H), 5.37(s, 1 H),5.90 (s, 1 H), 6.31(dd, J = 8.2, 2.2 Hz, 1 H), 6.35 (dd, J = 7.7, 1.6Hz, 1 H), 6.36(d, J = 2.2 Hz, 1 H), 6.50(td, J = 7.7, 1.6 Hz, 1 H),6.56(d, J = 8.1 Hz, 1 H), 6.66(d, J = 8.1 Hz, 1 H), 6.68(td, J = 7.7,1.2 Hz, 1 H), 6.73 (dd, J = 7.7, 1.2 Hz, 1 H), 6.84(d, J = 8.2 Hz, 1 H),9.36(s, 1 H)Using Reference Compound No. 3-2, the following Reference Compound (No.4-2) was obtained by a method similar to that of Reference Compound No.4-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.09(s, 3 H), 1.19(s, 3 H), 1.89(s, 3 H),2.04 (s, 3 H), 3.65(s, 3 H), 3.93(dd, J = 13.3, 6.7 Hz, 1 H),4.02-4.07(m, 1 H), 4.14-4.17(m, 1 H), 5.39(s, 1 H), 5.93(s, 1 H),6.06(dd, J = 12.1, 2.5 Hz, 1 H), 6.20(td, J = 8.4, 2.5 Hz, 1 H), 6.35(dd, J = 8.1, 2.2 Hz, 1 H), 6.42(d, J = 2.2 Hz, 1 H), 6.57(d, J = 8.2Hz, 1 H), 6.69(d, J = 8.2 Hz, 1 H), 6.86-6.89(m, 1 H), 6.93(d, J = 8.1Hz, 1 H), 9.41(s, 1 H)

Reference Example 56-(4-Hydroxy-2-methoxyphenyl)-5-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 5)

6-(4-Hydroxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 4-1, 37.7 mg, 0.0876 mmol) and sodium hydrogencarbonate (9.5 mg, 0.113 mmol) were dissolved in 1,4-dioxane (0.5mL)-water (0.5 mL), and then 9-fluorenylmethoxycarbonyl chloride (25.6mg, 0.0990 mmol) was added thereto under ice cooling. After the reactionmixture was stirred at room temperature for 3 hours, it was diluted withethyl acetate (10 mL). The mixture was washed with 1N aqueous HClsolution (10 mL), water (10 mL) and saturated brine (10 mL)successively, dried over anhydrous magnesium sulfate, and then thesolvent was removed under reduced pressure. The obtained residue waspurified by silica gel column chromatography (hexane-ethyl acetate) togive the titled reference compound (19.7 mg) as a colorless amorphousproduct. (Yield 34%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.22(s, 3 H), 1.28(s, 3 H), 2.20(s, 3 H),3.29 (s, 3 H), 3.61(s, 3 H), 3.89(s, 2 H), 5.30(d, J = 14.3 Hz, 1 H),5.45(s, 1 H), 5.81(d, J = 14.3 Hz, 1 H), 5.85(s, 1 H), 6.22(dd, J = 8.2,2.1 Hz, 1 H), 6.34-6.35(m, 2 H), 6.43(d, J = 8.3 Hz, 1 H), 6.63-6.65(m,2 H), 6.87-6.91(m, 3 H), 7.09- 7.25(m, 4 H), 7.31-7.35 (m, 2 H), 7.79(d,J = 7.6 Hz, 2 H), 9.32(s, 1 H)

Example 16-[4-(Furan-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Compound No. 1-1)

6-(4-Hydroxy-2-methoxyphenyl)-5-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 5, 17.4 mg, 0.0267 mmol) was dissolved inmethylene dichloride (0.5 mL), and then triethylamine (10 μL, 0.072mmol) and 2-furoyl chloride (3.6 μL, 0.036 mmol) were added theretosuccessively. After the reaction mixture was stirred at room temperaturefor 3 hours, the reaction mixture was purified by silica gel columnchromatography (hexane-ethyl acetate) to give a colorless amorphousproduct (15.6 mg). The obtained colorless amorphous product (11.8 mg)was dissolved in N,N-dimethylformamide (0.3 mL) and piperidine (15.6 μL,0.158 mmoL) was added thereto. After the reaction mixture was stirred atroom temperature for 1 minute, it was diluted with ethyl acetate (10mL). The reaction mixture was washed with water (10 mL) and saturatedbrine (10 mL) successively, dried over anhydrous magnesium sulfate, andthen the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled compound (6.0 mg) as a colorless solid.(Yield 76%)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.15(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.66 (s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.5, 3.3 Hz, 1 H), 4.05(dd, J= 12.5, 6.5 Hz, 1 H), 4.24 (dd, J = 6.5, 3.3 Hz, 1 H), 5.40(s, 1 H),6.01 (s, 1 H), 6.37(d, J = 7.8 Hz, 1 H), 6.51(t, J = 7.8 Hz, 1 H),6.61(d, J = 8.2 Hz, 1 H), 6.68(t, J = 7.8 Hz, 1 H), 6.73(d, J = 8.2 Hz,1 H), 6.74(d, J = 7.8 Hz, 1 H), 6.79(dd, J = 3.8, 1.3 Hz, 1 H), 6.83(dd, J = 8.0, 2.2 Hz, 1 H), 6.93(d, J = 2.2 Hz, 1 H), 7.15(d, J = 8.0Hz, 1 H), 7.55(d, J = 3.8 Hz, 1 H), 8.10(d, J = 1.3 Hz, 1 H)

6-[2-Methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Compound No. 1-2)

A mixture of6-(4-hydroxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 4-1, 25.0 mg, mmol), 2-methylnicotinoic acid(8.0 mg, 0.058 mmol), N,N-diisopropylethylamine (20.2 μL, 0.116 mmol)and O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate (24.3 mg, mmol) was dissolved in anhydrousN,N-dimethylformamide (0.5 mL), and then the reaction mixture wasstirred at room temperature overnight. The reaction mixture was dilutedwith ethyl acetate (70 mL). The mixture was washed with water (70 mL)and saturated brine (50 mL) successively, dried over anhydrous magnesiumsulfate, and then the solvent was removed under reduced pressure. Theobtained residue was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled compound (20.7 mg) as acolorless solid. (Yield 65%)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),2.78 (s, 3 H), 3.68(s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.4, 3.3 Hz, 1H), 4.07 (dd, J = 12.4, 6.9 Hz, 1 H), 4.26(dd, J = 6.9, 3.3 Hz, 1 H),5.40(s, 1 H), 6.02(s, 1 H), 6.38 (dd, J = 7.8, 1.2 Hz, 1 H), 6.52(td, J= 7.8, 1.2 Hz, 1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.8, 1.2 Hz,1 H), 6.73 (d, J = 8.2 Hz, 1 H), 6.75 (dd, J = 7.8, 1.2 Hz, 1 H),6.88(dd, J = 8.2, 2.3 Hz, 1 H), 7.00(d, J = 2.3 Hz, 1 H), 7.17(d, J =8.2 Hz, 1 H), 7.45(dd, J = 7.9, 4.8 Hz, 1 H), 8.43 (dd, J = 7.9, 1.8 Hz,1 H), 8.70(dd, J = 4.8, 1.8 Hz, 1 H)

6-(4-Benzoyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Compound No. 1-3)

6-(4-Hydroxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 4-1, 25.0 mg, 0.0581 mmol) was dissolved inmethylene dichloride (0.5 mL), and then triethylamine (16.2 μL, 0.116mmol) and benzoyl chloride (8.7 μL, 0.075 mmol) were added theretosuccessively under ice cooling. The reaction mixture was stirred underice cooling for 30 minutes. The reaction mixture was purified by silicagel column chromatography (hexane-ethyl acetate) to give the titledcompound (13.0 mg) as a colorless amorphous product. (Yield 65%)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.4, 3.4 Hz, 1 H), 4.07(dd, J= 12.4, 6.4 Hz, 1 H), 4.26 (dd, J = 6.4, 3.4 Hz, 1 H), 5.40(s, 1 H),6.02 (s, 1 H), 6.38(dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3Hz, 1 H), 6.62(d, J = 8.3 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz, 1 H),6.74(d, J = 8.3 Hz, 1 H), 6.75(dd, J = 7.8, 1.3 Hz, 1 H), 6.85 (dd, J =8.1, 2.2 Hz, 1 H), 6.97(d, J = 2.2 Hz, 1 H), 7.16(d, J = 8.1 Hz, 1 H),7.61(t, J = 7.5 Hz, 2 H), 7.75(t, J = 7.5 Hz, 1 H), 8.13(d, J = 7.5 Hz,2 H)Using any compounds among Reference Compounds No. 4- or 5, the followingCompounds (No. 1-4˜1-45) were obtained by a method similar to that ofCompound No. 1-1, 1-2 or 1-3.

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.06(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.85-3.88(m, 1 H), 3.86 (s, 3 H),4.05-4.09(m, 1 H), 4.24-4.26(m, 1 H), 5.40(s, 1 H), 6.01(s, 1 H),6.38(dd, J = 7.7, 1.2 Hz, 1 H), 6.52(td, J = 7.7, 1.2 Hz, 1 H), 6.62(d,J = 8.2 Hz, 1 H), 6.69(td, J = 7.7, 1.2 Hz, 1 H), 6.73 (d, J = 8.2 Hz, 1H), 6.73- 6.75(m, 1 H), 6.80(dd, J = 8.0, 2.3 Hz, 1 H), 6.89 (d, J = 2.3Hz, 1 H), 7.07- 7.10(m, 1 H), 7.15(d, J = 8.0 Hz, 1 H), 7.22(d, J = 7.9Hz, 1 H), 7.63(td, J = 7.9, 1.7 Hz, 1 H), 7.90 (dd, J = 7.9, 1.7 Hz, 1H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.03(s, 3 H), 1.22(s, 3 H), 2.06(s, 3 H),2.59 (s, 3 H), 3.68(s, 3 H), 3.72(s, 3 H), 3.85-3.88 (m, 1 H),4.05-4.07(m, 1 H), 4.25-4.26(m, 1 H), 5.40(s, 1 H), 6.02(s, 1 H),6.39(d, J = 7.8 Hz, 1 H), 6.52(t, J = 7.8 Hz, 1 H), 6.63(d, J = 8.2 Hz,1 H), 6.70(t, J = 7.8 Hz, 1 H), 6.74(d, J = 8.2 Hz, 1 H), 6.75(d, J =7.8 Hz, 1 H), 6.85(dd, J = 8.2, 2.2 Hz, 1 H), 6.96(d, J = 2.2 Hz, 1 H),7.15(d, J = 8.2 Hz, 1 H), 7.37-7.42(m, 2 H), 7.56(t, J = 7.7 Hz, 1 H),8.07(d, J = 7.7 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.15(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.66 (s, 3 H), 3.72(s, 3 H), 3.81-3.84(m, 1 H), 4.02- 4.05(m, 1 H),4.24-4.26 (m, 1 H), 5.40(s, 1 H), 6.02(s, 1 H), 6.36(d, J = 7.7 Hz, 1H), 6.52(t, J = 7.7 Hz, 1 H), 6.62(d, J = 8.3 Hz, 1 H), 6.69(t, J = 7.7Hz, 1 H), 6.73(d, J = 8.3 Hz, 1 H), 6.73-6.75(m, 1 H), 6.80(dd, J = 8.2,2.3 Hz, 1 H), 6.89(d, J = 2.3 Hz, 1 H), 6.93(dd, J = 1.7, 0.8 Hz, 1 H),7.14(d, J = 8.2 Hz, 1 H), 7.90(t, J = 1.7 Hz, 1 H), 8.62(dd, J = 1.7,0.8 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.66 (s, 3 H), 3.72(s, 3 H), 3.83-3.86(m, 1 H), 4.05- 4.08(m, 1 H),4.24-4.26 (m, 1 H), 5.40(s, 1 H), 6.01(s, 1 H), 6.36(dd, J = 7.7, 1.3Hz, 1 H), 6.52 (td, J = 7.7, 1.3 Hz, 1 H), 6.62(d, J = 8.2 Hz, 1 H),6.69(td, J = 7.7, 1.3 Hz, 1 H), 6.74(d, J = 8.2 Hz, 1 H), 6.74(dd, J =7.7, 1.3 Hz, 1 H), 6.82(dd, J = 8.3, 2.1 Hz, 1 H), 6.92(d, J = 2.1 Hz, 1H), 7.15(d, J = 8.3 Hz, 1 H), 7.14(dd, J = 5.1, 1.4 Hz, 1 H), 7.74 (dd,J = 5.1, 2.9 Hz, 1 H), 8.59(dd, J = 2.9, 1.4 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.2, 3.3 Hz, 1 H),4.06-4.09(m, 1 H), 4.25(dd, J = 6.8, 3.3 Hz, 1 H), 5.40(s, 1 H), 6.02(s,1 H), 6.38(dd, J = 7.7, 1.4 Hz, 1 H), 6.52 (td, J = 7.7, 1.4 Hz, 1 H),6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.7, 1.4 Hz, 1 H), 6.74(d, J =8.2 Hz, 1 H), 6.74-6.76(m, 1 H), 6.90(dd, J = 8.3, 2.2 Hz, 1 H), 7.02(d,J = 2.2 Hz, 1 H), 7.17(d, J = 8.3 Hz, 1 H), 7.65(ddd, J = 7.9, 4.9, 0.9Hz, 1 H), 8.46 (dt, J = 7.9, 2.0 Hz, 1 H), 8.90(dd, J = 4.9, 2.0 Hz, 1H), 9.26(dd, J = 2.0, 0.9 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.91(s, 3 H),2.05 (s, 3 H), 3.74(s, 3 H), 3.95(dd, J = 13.1, 5.2 Hz, 1 H), 4.10(dd, J= 13.1, 4.2 Hz, 1 H), 4.25 (br s, 1 H), 5.41(s, 1 H), 6.04(s, 1 H),6.07(dd, J = 12.1, 2.5 Hz, 1 H), 6.21 (td, J = 8.4, 2.5 Hz, 1 H),6.63(d, J = 8.2 Hz, 1 H), 6.76(d, J = 8.2 Hz, 1 H), 6.86-6.90(m, 1 H),6.90(dd, J = 8.1, 2.4 Hz, 1 H), 7.04(d, J = 2.4 Hz, 1 H), 7.27(d, J =8.1 Hz, 1 H), 7.54-7.58(m, 1 H), 7.67-7.69(m, 2 H), 8.10(d, J = 7.3 Hz,1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.68 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.1, 2.8 Hz, 1 H),4.03-4.09(m, 1 H), 4.24-4.26(m, 1 H), 5.40(s, 1 H), 6.03(s, 1 H),6.38(d, J = 7.5 Hz, 1 H), 6.52(t, J = 7.5 Hz, 1 H), 6.62(d, J = 8.3 Hz,1 H), 6.69(t, J = 7.5 Hz, 1 H), 6.74(d, J = 8.3 Hz, 1 H), 6.74(d, J =7.5 Hz, 1 H), 6.88(dd, J = 8.2, 2.3 Hz, 1 H), 6.98(d, J = 2.3 Hz, 1 H),7.18(d, J = 8.2 Hz, 1 H), 7.53-7.57 (m, 1 H), 7.66-7.68(m, 2 H), 8.09(d,J = 7.6 Hz, 1 H)

¹H-NMR (400 MHz, CDCl₃) δ 1.04(t, J = 7.3 Hz, 3 H), 1.25(s, 3 H), 1.29(s, 3 H), 1.79(sept, J = 7.3 Hz, 2 H), 2.17(s, 3 H), 2.53(t, J = 7.3 Hz,2 H), 3.66(s, 3 H), 3.75(s, 3 H), 3.87(br s, 1 H), 4.01 (d, J = 12.3 Hz,1 H), 4.14 (d, J = 12.3 Hz, 1 H), 4.34 (br s, 1 H), 5.46(s, 1 H),6.38(dd, J = 7.8, 1.5 Hz, 1 H), 6.55-6.59(m, 1 H), 6.56(d, J = 8.1 Hz, 1H), 6.59(d, J = 2.2 Hz, 1 H), 6.67(dd, J = 8.1, 2.2 Hz, 1 H), 6.69(dd, J= 7.8, 1.5 Hz, 1 H), 6.77(td, J = 7.8, 1.5 Hz, 1 H), 6.85(d, J = 8.1 Hz,1 H), 7.14(d, J = 8.1 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.7, 3.3 Hz, 1 H), 4.07(dd, J= 12.7, 6.5 Hz, 1 H), 4.25 (dd, J = 6.5, 3.3 Hz, 1 H), 5.40(s, 1 H),6.03(s, 1 H), 6.38(dd, J = 7.6, 1.2 Hz, 1 H), 6.52(td, J = 7.6, 1.2 Hz,1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.6, 1.2 Hz, 1 H), 6.74 (d,J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.6, 1.2 Hz, 1 H), 6.86(dd, J = 8.1, 2.3Hz, 1 H), 6.97(d, J = 2.3 Hz, 1 H), 7.16(d, J = 8.1 Hz, 1 H),7.39-7.46(m, 2 H), 7.75-7.80(m, 1 H), 8.10 (td, J = 7.7, 1.8 Hz, 1 H)

¹H-NMR(400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.3, 3.5 Hz, 1 H), 4.07(dd, J= 12.3, 7.0 Hz, 1 H), 4.25(dd, J = 7.0, 3.5 Hz, 1 H), 5.40(s, 1 H),6.03(s, 1 H), 6.38(dd, J = 7.8, 1.3 Hz, 1 H), 6.52(td, J = 7.8, 1.3 Hz,1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d,J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.90(dd, J = 8.1, 2.2Hz, 1 H), 7.02(d, J = 2.2 Hz, 1 H), 7.18(d, J = 8.1 Hz, 1 H), 8.00(d, J= 6.1 Hz, 2 H), 8.88(d, J = 6.1 Hz, 2 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.15(s, 3 H), 1.21(s, 3 H), 1.22(d, J = 6.8Hz, 6 H), 2.06(s, 3 H), 2.78 (hept, J = 6.8 Hz, 1 H), 3.65(s, 3 H),3.71(s, 3 H), 3.82(dd, J = 12.4, 3.2 Hz, 1 H), 4.04(dd, J = 12.4, 6.7Hz, 1 H), 4.23 (dd, J = 6.7, 3.2 Hz, 1 H), 5.39(s, 1 H), 6.01(s, 1 H),6.35(dd, J = 7.8, 1.6 Hz, 1 H), 6.51(td, J = 7.8, 1.6 Hz, 1 H), 6.60(d,J = 8.3 Hz, 1 H), 6.67(dd, J = 8.1, 2.1 Hz, 1 H), 6.68-6.72(m, 1 H),6.71 (d, J = 8.3 Hz, 1 H), 6.74 (dd, J = 7.8, 1.6 Hz, 1 H), 6.75(d, J =2.1 Hz, 1 H), 7.10(d, J = 8.1 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.2, 3.5 Hz, 1 H),4.04-4.08(m, 1 H), 4.24(dd, J = 6.6, 3.5 Hz, 1 H), 5.40(s, 1 H), 6.03(s,1 H), 6.37(dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J = 7.8, 1.3 Hz, 1 H),6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz, 1 H), 6.73(d, J =8.2 Hz, 1 H), 6.74(dd, J = 7.8, 1.3 Hz, 1 H), 6.84(dd, J = 8.1, 2.3 Hz,1 H), 6.94(d, J = 2.3 Hz, 1 H), 7.15(d, J = 8.1 Hz, 1 H), 7.31(dd, J =5.0, 3.7 Hz, 1 H), 8.01 (dd, J = 3.7, 1.3 Hz, 1 H), 8.09(dd, J = 5.0,1.3 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.12(s, 3 H), 1.20(s, 3 H), 1.92(s, 3 H),2.05 (s, 3 H), 3.72(s, 3 H), 3.95(dd, J = 13.1, 4.6 Hz, 1 H), 4.10(dd, J= 13.1, 4.6 Hz, 1 H), 4.24 (t, J = 4.6 Hz, 1 H), 5.41 (s, 1 H), 6.03(s,1 H), 6.08(dd, J = 12.4, 2.5 Hz, 1 H), 6.21(td, J = 8.4, 2.5 Hz, 1 H),6.63(d, J = 8.2 Hz, 1 H), 6.77(d, J = 8.2 Hz, 1 H), 6.87-6.90 (m, 1 H),6.92(dd, J = 8.1, 2.3 Hz, 1 H), 7.08(d, J = 2.3 Hz, 1 H), 7.27(d, J =8.1 Hz, 1 H), 7.66 (ddd, J = 8.0, 4.9, 0.9 Hz, 1 H), 8.47(dt, J = 8.0,2.0 Hz, 1 H), 8.90 (dd, J = 4.9, 2.0 Hz, 1 H), 9.27(dd, J = 2.0, 0.9 Hz,1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.90(s, 3 H),2.05 (s, 3 H), 3.71(s, 3 H), 3.93(dd, J = 13.1, 4.2 Hz, 1 H), 4.09(dd, J= 13.1, 4.2 Hz, 1 H), 4.24 (t, J = 4.2 Hz, 1 H), 5.41 (s, 1 H), 6.04(s,1 H), 6.06(dd, J = 12.7, 2.6 Hz, 1 H), 6.21(td, J = 8.5, 2.6 Hz, 1 H),6.62(d, J = 8.2 Hz, 1 H), 6.75(d, J = 8.2 Hz, 1 H), 6.80(dd, J = 3.6,1.7 Hz, 1 H), 6.84-6.90(m, 2 H), 6.99 (d, J = 2.2 Hz, 1 H), 7.24 (d, J =8.3 Hz, 1 H), 7.57 (dd, J = 3.6, 0.8 Hz, 1 H), 8.11(dd, J = 1.7, 0.8 Hz,1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.87(dd, J = 12.4, 3.3 Hz, 1 H), 3.91(s, 3H), 4.07(dd, J = 12.4, 6.6 Hz, 1 H), 4.26(dd, J = 6.6, 3.3 Hz, 1 H),5.40(s, 1 H), 6.02(s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52(td, J= 7.8, 1.3 Hz, 1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.70(td, J = 7.8, 1.3 Hz,1 H), 6.75(d, J = 8.2 Hz, 1 H), 6.75(d, J = 7.8, 1.3 Hz, 1 H), 6.89 (dd,J = 8.1, 2.3 Hz, 1 H), 7.01(d, J = 2.3 Hz, 1 H), 7.17(d, J = 8.1 Hz, 1H), 7.78(t, J = 7.8 Hz, 1 H), 8.30(dt, J = 7.8, 1.5 Hz, 1 H), 8.38(dt, J= 7.8, 1.5 Hz, 1 H), 8.64(t, J = 1.5 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),2.41 (s, 3 H), 3.67(s, 3 H), 372(s, 3 H), 3.85(dd, J = 12.7, 3.4 Hz, 1H), 4.07 (dd, J = 12.7, 6.8 Hz, 1 H), 4.25(dd, J = 6.8, 3.4 Hz, 1 H),5.40(s, 1 H), 6.02(s, 1 H), 6.38(dd, J = 7.8, 1.4 Hz, 1 H), 6.52 (td, J= 7.8, 1.4 Hz, 1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.8, 1.4 Hz,1 H), 6.74(d, J = 8.2 Hz, 1 H), 6.75(dd, J = 7.8, 1.4 Hz, 1 H), 6.84(dd,J = 8.1, 2.4 Hz, 1 H), 6.95(d, J = 2.4 Hz, 1 H), 7.16(d, J = 8.1 Hz, 1H), 7.49(t, J = 7.7 Hz, 1 H), 7.56(d, J = 7.7 Hz, 1 H), 7.92(d, J = 7.7Hz, 1 H), 7.95(s, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),2.42 (s, 3 H), 3.67(s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.2, 3.5 Hz, 1H), 4.07 (dd, J = 12.2, 6.3 Hz, 1 H), 4.25(dd, J = 6.3, 3.5 Hz, 1 H),5.40(s, 1 H), 6.01(s, 1 H), 6.38(dd, J = 7.7, 1.3 Hz, 1 H), 6.52 (td, J= 7.7, 1.3 Hz, 1 H), 6.62(d, J = 8.1 Hz, 1 H), 6.69(td, J = 7.7, 1.3 Hz,1 H), 6.74(d, J = 8.1 Hz, 1 H), 6.74(dd, J = 7.7, 1.3 Hz, 1 H), 6.84(dd,J = 8.2, 2.2 Hz, 1 H), 6.94(d, J = 2.2 Hz, 1 H), 7.15(d, J = 8.2 Hz, 1H), 7.41(d, J = 8.4 Hz, 2 H), 8.02(d, J = 8.4 Hz, 2 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.3, 3.3 Hz, 1 H), 4.07(dd, J= 12.3, 6.5 Hz, 1 H), 4.25 (dd, J = 6.5, 3.3 Hz, 1 H), 5.40(s, 1 H),6.02(s, 1 H), 6.38(dd, J = 7.7, 1.3 Hz, 1 H), 6.52(td, J = 7.7, 1.3 Hz,1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.7, 1.3 Hz, 1 H), 6.74 (d,J = 8.2 Hz, 1 H), 6.75 dd, J = 7.7, 1.3 Hz, 1 H), 6.88(dd, J = 8.3, 2.2Hz, 1 H), 7.00(d, J = 2.2 Hz, 1 H), 7.17(d, J = 8.3 Hz, 1 H), 7.65(t, J= 8.0 Hz, 1 H), 7.83(ddd, J = 8.0, 2.2, 1.1 Hz, 1 H), 8.07- 8.09(m, 1H), 8.10-8.11 (m, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.66 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.5, 3.5 Hz, 1 H), 3.87(s, 3H), 4.07(dd, J = 12.5, 6.5 Hz, 1 H), 4.25(dd, J = 6.5, 3.5 Hz, 1 H),5.40(s, 1 H), 6.01(s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52(td, J= 7.8, 1.3 Hz, 1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz,1 H), 6.74(d, J = 8.2 Hz, 1 H), 6.74(dd, J = 7.8, 1.3 Hz, 1 H), 6.82(dd, J = 8.2, 2.4 Hz, 1 H), 6.92(d, J = 2.4 Hz, 1 H), 7.12(d, J = 9.0Hz, 2 H), 7.14(d, J = 8.2 Hz, 1 H), 8.08(d, J = 9.0 Hz, 2 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.2, 3.1 Hz, 1 H), 4.07(dd, J= 12.2, 6.6 Hz, 1 H), 4.25 (dd, J = 6.6, 3.1 Hz, 1 H), 5.40(s, 1 H),6.02(s, 1 H), 6.38(dd, J = 7.8, 1.3 Hz, 1 H), 6.52(td, J = 7.8, 1.3 Hz,1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d,J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.85(dd, J = 8.0, 2.4Hz, 1 H), 6.97(d, J = 2.4 Hz, 1 H), 7.16(d, J = 8.0 Hz, 1 H),7.41-7.47(m, 2 H), 8.18-8.23(m, 2 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.2, 3.4 Hz, 1 H), 4.07(dd, J= 12.2, 6.7 Hz, 1 H), 4.25 (dd, J = 6.7, 3.4 Hz, 1 H0, 5.40(s, 1 H),6.02(s, 1 H), 6.38(dd, J = 7.8, 1.3 Hz, 1 H), 6.52(td, J = 7.8, 1.3 Hz,1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d,J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.86(dd, J = 8.1, 2.2Hz, 1 H), 6.98(d, J = 2.2 Hz, 1 H), 7.16(d, J = 8.1 Hz, 1 H), 7.68(d, J= 8.8 Hz, 2 H), 8.13(d, J = 8.8 Hz, 2 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.68 (s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.3, 3.0 Hz, 1 H), 4.06(dd, J= 12.3, 6.7 Hz, 1 H), 4.24 (dd, J = 6.7, 3.0 Hz, 1 H), 5.40(s, 1 H),6.04(s, 1 H), 6.37(dd, J = 7.8, 1.3 Hz, 1 H), 6.51(td, J = 7.8, 1.3 Hz,1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.68(td, J = 7.8, 1.3 Hz, 1 H), 6.73 (d,J = 8.2 Hz, 1 H), 6.74 (dd, J = 7.8, 1.3 Hz, 1 H), 6.85(dd, J = 8.1, 2.2Hz, 1 H), 6.94(d, J = 2.2 Hz, 1 H), 7.20(d, J = 8.1 Hz, 1 H), 7.90(td, J= 7.6, 1.6 Hz, 1 H), 7.95(td, J = 7.6, 1.6 Hz, 1 H), 8.10 (dd, J = 7.6,1.6 Hz, 1 H), 8.18(dd, J = 7.6, 1.6 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),2.46 (s, 3 H), 3.67(s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 13.0, 3.4 Hz, 1H), 4.07 (dd, J = 13.0, 6.9 Hz, 1 H), 4.25(dd, J = 6.9, 3.4 Hz, 1 H),5.40(s, 1 H), 6.03(s, 1 H), 6.38(dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J= 7.8, 1.3 Hz, 1 H), 6.62(d, J = 8.1 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz,1 H), 6.74(d, J = 8.1 Hz, 1 H), 6.74(dd, J = 7.8, 1.3 Hz, 1 H), 6.83(dd,J = 8.2, 2.2 Hz, 1 H), 6.94(d, J = 2.2 Hz, 1 H), 7.16(d, J = 8.2 Hz, 1H), 7.31(td, J = 7.8, 1.5 Hz, 1 H), 7.46 (dd, J = 7.8, 1.5 Hz, 1 H),7.66(td, J = 7.8, 1.5 Hz, 1 H), 8.17(dd, J = 7.8, 1.5 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),2.67 (s, 3 H), 3.67(s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.3, 3.1 Hz, 1H), 4.08 (dd, J = 12.3, 6.7 Hz, 1 H), 4.26(dd, J = 6.7, 3.1 Hz, 1 H),5.40(s, 1 H), 6.02(s, 1 H), 6.38 (dd, J = 7.8, 1.3 Hz, 1 H), 6.52(td, J= 7.8, 1.3 Hz, 1 H), 6.62(d, J = 8.1 Hz, 1 H), 6.70(td, J = 7.8, 1.3 Hz,1 H), 6.75 (d, J = 8.1 Hz, 2 H), 6.89 (dd, J = 8.2, 2.3 Hz, 1 H),7.00(d, J = 2.3 Hz, 1 H), 7.18(d, J = 8.2 Hz, 1 H), 7.77(t, J = 7.8 Hz,1 H), 8.31(dt, J = 7.8, 1.5 Hz, 1 H), 8.36(dt, J = 7.8, 1.5 Hz, 1 H),8.61 (t, J = 1.5 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 12.2, 3.4 Hz, 1 H), 4.06(dd, J= 12.2, 6.6 Hz, 1 H), 4.24 (dd, J = 6.6, 3.4 Hz, 1 H), 5.40(s, 1 H),6.03(s, 1 H), 6.37(dd, J = 7.8, 1.4 Hz, 1 H), 6.52(td, J = 7.8, 1.4 Hz,1 H), 6.62(d, J = 8.3 Hz, 1 H), 6.69(td, J = 7.8, 1.4 Hz, 1 H), 6.73 (d,J = 8.3 Hz, 1 H), 6.75 (dd, J = 7.8, 1.4 Hz, 1 H), 6.84(dd, J = 8.3, 2.2Hz, 1 H), 6.96(d, J = 2.2 Hz, 1 H), 7.15(d, J = 8.3 Hz, 1 H), 7.35(d, J= 5.2 Hz, 1 H), 8.14(d, J = 5.2 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.15(s, 3 H), 1.22(s, 3 H), 2.07(s, 3 H),2.36 (s, 3 H), 3.66(s, 3 H), 3.72(s, 3 H), 3.87(dd, J = 12.4, 3.5 Hz, 1H), 4.06 (dd, J = 12.4, 6.9 Hz, 1 H), 4.24(dd, J = 6.9, 3.5 Hz, 1 H),5.39(s, 1 H), 6.01(s, 1 H), 6.37(dd, J = 7.7, 1.4 Hz, 1 H), 6.51 (td, J= 7.7, 1.4 Hz, 1 H), 6.61(d, J = 7.9 Hz, 1 H), 6.69(d, J = 1.4 Hz, 1 H),6.69(td, J = 7.7, 1.4 Hz, 1 H), 6.73(d, J = 7.9 Hz, 1 H), 6.74(dd, J =7.7, 1.4 Hz, 1 H), 6.81(dd, J = 8.0, 2.2 Hz, 1 H), 6.92(d, J = 2.2 Hz, 1H), 7.14(d, J = 8.0 Hz, 1 H), 7.94(d, J = 1.4 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.86(dd, J = 11.8, 3.5 Hz, 1 H), 4.07(dd, J= 11.8, 6.8 Hz, 1 H), 4.24 (dd, J = 6.8, 3.5 Hz, 1 H), 5.40(s, 1 H),6.02(s, 1 H), 6.37(dd, J = 7.8, 1.3 Hz, 1 H), 6.52(td, J = 7.8, 1.3 Hz,1 H), 6.62(d, J = 8.1 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz, 1 H), 6.74 (d,J = 8.1 Hz, 2 H), 6.85 (dd, J = 8.2, 2.2 Hz, 1 H), 6.95(d, J = 2.2 Hz, 1H), 7.16(d, J = 8.2 Hz, 1 H), 8.86(d, J = 2.0 Hz, 1 H), 9.27(d, J = 2.0Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),2.60 (s, 3 H), 3.67(s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.1, 3.4 Hz, 1H), 4.07 (dd, J = 12.1, 6.4 Hz, 1 H), 4.25(dd, J = 6.4, 3.4 Hz, 1 H),5.40(s, 1 H), 6.02(s, 1 H), 6.37(dd, J = 7.8, 1.3 Hz, 1 H), 6.52 (td, J= 7.8, 1.3 Hz, 1 H), 6.62(d, J = 8.1 Hz, 1 H), 6.69(td, J = 7.8, 1.3 Hz,1 H), 6.74(d, J = 8.1 Hz, 1 H), 6.74(dd, J = 7.8, 1.3 Hz, 1 H), 6.87(dd,J = 8.1, 2.3 Hz, 1 H), 6.99(d, J = 2.3 Hz, 1 ), 7.16(d, J = 8.1 Hz, 1H), 7.50(d, J = 8.2 Hz, 1 H), 8.33(dd, J = 8.2, 2.4 Hz, 1 H), 9.12 (d, J= 2.4 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.16(s, 3 H), 1.22(s, 3 H), 2.08(s, 3 H),3.67 (s, 3 H), 3.72(s, 3 H), 3.85(dd, J = 12.7, 3.1 Hz, 1 H), 3.97(s, 3H), 4.07(dd, J = 12.7, 6.8 Hz, 1 H), 4.25(dd, J = 6.8, 3.1 Hz, 1 H),5.40(s, 1 H), 6.02(s, 1 H), 6.37 (dd, J = 7.7, 1.3 Hz, 1 H), 6.52(td, J= 7.7, 1.3 Hz, 1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.69(td, J = 7.7, 1.3 Hz,1 H), 6.73(d, J = 8.2 Hz, 1 H), 6.74(dd, J = 7.7, 1.3 Hz, 1 H), 6.82(dd, J = 8.1, 2.2 Hz, 1 H), 6.93(d, J = 2.2 Hz, 1 H), 7.15(d, J = 8.1Hz, 1 H), 7.19(dd, J = 7.5, 4.9 Hz, 1 H), 8.39(dd, J = 7.5, 2.1 Hz, 1H), 8.47(dd, J = 4.9, 2.1 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.90(s, 3 H),2.05 (s, 3 H), 3.71(s, 3 H), 3.93(dd, J = 13.2, 4.6 Hz, 1 H), 4.08(dd, J= 13.2, 4.6 Hz, 1 H), 4.20- 4.25(m, 1 H), 5.41(s, 1 H), 6.03(s, 1 H),6.06 (dd, J = 12.2, 2.5 Hz, 1 H), 6.21(td, J = 8.4, 2.5 Hz, 1 H),6.62(d, J = 8.2 Hz, 1 H), 6.75(d, J = 8.2 Hz, 1 H), 6.83(dd, J = 8.1,2.2 Hz, 1 H), 6.86- 6.90(m, 1 H), 6.94(dd, J = 1.7, 0.9 Hz, 1 H), 6.96(d, J = 2.2 Hz, 1 H), 7.23 (d, J = 8.1 Hz, 1 H), 7.91 (t, J = 1.7 Hz, 1H), 8.63 (dd, J = 1.7, 0.9 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.12(s, 3 H), 1.20(s, 3 H), 1.91(s, 3 H),2.05 (s, 3 H), 3.72(s, 3 H), 3.94(dd, J = 13.1, 4.9 Hz, 1 H), 4.10(dd, J= 13.1, 4.2 Hz, 1 H), 4.23- 4.26(m, 1 H), 5.41(s, 1 H), 6.04(s, 1 H),6.07 (dd, J = 12.2, 2.4 Hz, 1 H), 6.21(td, J = 8.4, 2.4 Hz, 1 H),6.63(d, J = 8.2 Hz, 1 H), 6.76(d, J = 8.2 Hz, 1 H), 6.86-6.90(m, 1 H),6.92(dd, J = 8.3, 2.2 Hz, 1 H), 7.08(d, J = 2.2 Hz, 1 H), 7.27(d, J =8.3 Hz, 1 H), 8.01(d, J = 6.1 Hz, 2 H), 8.89(d, J = 6.1 Hz, 2 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.91(s, 3 H),2.05 (s, 3 H), 3.73(s, 3 H), 3.95(dd, J = 13.4, 4.8 Hz, 1 H), 4.10(dd, J= 13.4, 4.2 Hz, 1 H), 4.22- 4.27(m, 1 H), 5.41(s, 1 H), 6.03(s, 1 H),6.07 (dd, J = 12.2, 2.6 Hz, 1 H), 6.21(td, J = 8.5, 2.6 Hz, 1 H),6.62(d, J = 8.3 Hz, 1 H), 6.76(d, J = 8.3 Hz, 1 H), 6.85-6.91(m, 1 H),6.89(dd, J = 8.2, 2.2 Hz, 1 H), 7.03(d, J = 2.2 Hz, 1 H), 7.26(d, J =8.2 Hz, 1 H), 7.40-7.47(m, 2 H), 7.75-7.81(m, 1 H), 8.11(td, J = 7.8,1.6 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.91(s, 3 H),2.05 (s, 3 H), 3.72(s, 3 H), 3.94(dd, J = 13.0, 5.0 Hz, 1 H), 4.09(dd, J= 13.0, 4.2 Hz, 1 H), 4.22- 4.26(m, 1 H), 5.41(s, 1 H), 6.03(s, 1 H),6.07 (dd, J = 12.2, 2.5 Hz, 1 H), 6.21(td, J = 8.4, 2.5 Hz, 1 H),6.62(d, J = 8.2 Hz, 1 H), 6.76(d, J = 8.2 Hz, 1 H), 6.86-6.90(m, 1 H),6.87(dd, J = 8.2, 2.3 Hz, 1 H), 7.00(d, J = 2.3 Hz, 1 H), 7.24(d, J =8.2 Hz, 1 H), 7.31(dd, J = 5.0, 3.7 Hz, 1 H), 8.02 (dd, J = 3.7, 1.3 Hz,1 H), 8.10(dd, J = 5.0, 1.3 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.91(s, 3 H),2.05 (s, 3 H), 3.72(s, 3 H), 3.94(dd, J = 12.9, 5.0 Hz, 1 H), 4.10(dd, J= 12.9, 3.9 Hz, 1 H), 4.23- 4.26(m, 1 H), 5.41(s, 1 H), 6.03(s, 1 H),6.07 (dd, J = 12.2, 2.5 Hz, 1 H), 6.21(td, J = 8.5, 2.5 Hz, 1 H),6.62(d, J = 8.1 Hz, 1 H), 6.76(d, J = 8.1 Hz, 1 H), 6.86-6.91(m, 1 H),6.88(dd, J = 8.3, 2.2 Hz, 1 H), 7.03(d, J = 2.2 Hz, 1 H), 7.25(d, J =8.3 Hz, 1 H), 7.45(t, J = 9.0 Hz, 2 H), 8.21(dd, J = 9.0, 5.5 Hz, 2 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.92(s, 3 H),2.05 (s, 3 H), 2.80(s, 3 H), 3.73(s, 3 H), 3.95(dd, J = 13.0, 5.0 Hz, 1H), 4.10 (dd, J = 13.0, 4.4 Hz, 1 H), 4.24-4.26(m, 1 H), 5.41(s, 1 H0,6.03(s, 1 H), 6.07(dd, J = 11.9, 2.5 Hz, 1 H), 6.63(d, J = 8.1 Hz, 1 H),6.76(d, J = 8.1 Hz, 1 H), 6.86-6.90 (m, 1 H), 6.91(dd, J = 8.1, 2.3 Hz,1 H), 7.06(d, J = 2.3 Hz, 1 H), 7.26(d, J = 8.1 Hz, 1 H), 7.46(dd, J =7.9, 5.0 Hz, 1 H0, 8.44 (dd, J = 7.9, 1.8 Hz, 1 H), 8.71(dd, J = 5.0,1.8 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.91(s, 3 H),2.05 (s, 3 H), 2.47(s, 3 H), 3.72(s, 3 H), 3.95(dd, J = 13.3, 4.5 Hz, 1H), 4.10 (dd, J = 13.3, 4.3 Hz, 1 H), 4.23-4.26(m, 1 H), 5.41(s, 1 H),6.03(s, 1 H), 6.08(dd, J = 12.1, 2.5 Hz, 1 H), 6.21(td, J = 8.4, 2.5 Hz,1 H), 6.63(d, J = 8.2 Hz, 1 H), 6.76(d, J = 8.2 Hz, 1 H), 6.86(dd, J =8.1, 2.1 Hz, 1 H), 6.86-6.90(m, 1 H), 6.99 (d, J = 2.1 Hz, 1 H), 7.25(d, J = 8.1 Hz, 1 H), 7.32 (t, J = 8.0 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 1H), 7.67 (td, J = 8.0, 1.6 Hz, 1 H), 8.18(dd, J = 8.0, 1.6 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.92(s, 3 H),2.05 (s, 3 H), 3.73(s, 3 H), 3.92(s, 3 H), 3.95(dd, J = 13.1, 4.9 Hz, 1H), 4.10 (dd, J = 13.1, 4.3 Hz, 1 H), 4.23-4.25(m, 1 H), 5.41(s, 1 H),6.03(s, 1 H), 6.08(dd, J = 12.1, 2.5 Hz, 1 H), 6.21(td, J = 8.4, 2.5 Hz,1 H), 6.63(d, J = 8.1 Hz, 1 H), 6.77(d, J = 8.1 Hz, 1 H), 6.87-6.90 (m,1 H), 6.91(dd, J = 8.2, 2.1 Hz, 1 H), 7.07(d, J = 2.1 Hz, 1 H), 7.27(d,J = 8.2 Hz, 1 H), 7.79(t, J = 7.8 Hz, 1 H), 8.31(dt, J = 7.8, 1.5 Hz, 1H), 8.39 (dt, J = 7.8, 1.5 Hz, 1 H), 8.65(t, J = 1.5 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.20(s, 3 H), 1.91(s, 3 H),2.05 (s, 3 H), 3.72(s, 3 H), 3.95(dd, J = 13.2, 4.3 Hz, 1 H), 3.97(s, 3H), 4.09(dd, J = 13.2, 4.3 Hz, 1 H), 4.23(t, J = 4.3 Hz, 1 H), 5.41(s, 1H), 6.02(s, 1 H), 6.07(dd, J = 12.2, 2.4 Hz, 1 H), 6.21 (td, J = 8.4,2.4 Hz, 1 H), 6.62(d, J = 8.2 Hz, 1 H), 6.76(d, J = 8.2 Hz, 1 H),6.85(dd, J = 8.0, 2.2 Hz, 1 H), 6.87-6.90(m, 1 H), 6.98(d, J = 2.2 Hz, 1H), 7.19(dd, J = 7.6, 4.9 Hz, 1 H), 7.25(d, J = 8.0 Hz, 1 H), 8.40(dd, J= 7.6, 2.0 Hz, 1 H), 8.47(dd, J = 4.9, 2.0 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.11(s, 3 H), 1.19(s, 3 H), 1.91(s, 3 H),2.04 (s, 3 H), 2.38(s, 3 H), 3.72(s, 3 H), 3.94(dd, J = 12.9, 4.3 Hz, 1H), 4.10 (dd, J = 12.9, 4.3 Hz, 1 H), 4.24(t, J = 4.3 Hz, 1 H), 5.41(s,1 H), 6.03 (s, 1 H), 6.06(dd, J = 12.2, 2.5 Hz, 1 H), 6.20 (td, J = 8.5,2.5 Hz, 1 H), 6.62(d, J = 8.3 Hz, 1 H), 6.69(d, J = 1.7 Hz, 1 H),6.75(d, J = 8.3 Hz, 1 H), 6.84(dd, J = 8.2, 2.3 Hz, 1 H), 6.86-6.90(m, 1H), 6.98(d, J = 2.3 Hz, 1 H), 7.23(d, J = 8.2 Hz, 1 H), 7.95(d, J = 1.7Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.15(s, 3 H), 1.21(s, 3 H), 2.06(s, 3 H),2.90 (s, 3 H), 3.02(s, 3 H), 3.64(s, 3 H), 3.71(s, 3 H), 3.82(dd, J =12.1, 3.3 Hz, 1 H), 4.04(dd, J = 12.1, 6.8 Hz, 1 H), 4.23 (dd, J = 6.8,3.3 Hz, 1 H), 5.39(s, 1 H), 5.99(s, 1 H), 6.35(dd, J = 7.8, 1.3 Hz, 1H), 6.51(td, J = 7.8, 1.3 Hz, 1 H), 6.60(d, J = 8.3 Hz, 1 H), 6.67(dd, J= 7.8, 1.3 Hz, 1 H), 6.68 (td, J = 7.8, 1.3 Hz, 1 H), 6.70(d, J = 8.3Hz, 1 H), 6.74(dd, J = 8.1, 1.8 Hz, 1 H), 6.75(d, J = 1.8 Hz, 1 H),7.06(d, J = 8.1 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.15(s, 3 H), 1.21(s, 3 H), 2.07(s, 3 H),3.38- 3.43(m, 2 H), 3.54-3.59 (m, 2 H), 3.61-3.64(m, 4 H), 3.64(s, 3 H),3.71 (s, 3 H), 3.82(dd, J = 13.1, 3.7 Hz, 1 H), 4.04 (dd, J = 13.1, 6.6Hz, 1 H), 4.23(dd, J = 6.6, 3.7 Hz, 1 H), 5.39(s, 1 H), 5.99(s, 1 H),6.35(dd, J = 7.7, 1.3 Hz, 1 H), 6.51 (td, J = 7.7, 1.3 Hz, 1 H), 6.60(d,J = 8.3 Hz, 1 H), 6.65-6.75(m, 4 H), 6.78 (d, J = 2.2 Hz, 1 H), 7.07 (d,J = 8.3 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.10(s, 3 H), 1.19(s, 3 H), 1.90(s, 3 H),2.04 (s, 3 H), 3.38-3.44(m, 2 H), 3.54-3.60(m, 2 H), 3.63-3.66(m, 4 H),3.70 (s, 3 H), 3.91(dd, J = 13.2, 4.8 Hz, 1 H), 4.06 (dd, J = 13.2, 4.8Hz, 1 H), 4.19-4.23(m, 1 H), 5.40(s, 1 H), 6.01(s, 1 H), 6.04(dd, J =12.1, 2.5 Hz, 1 H), 6.20(td, J = 8.4, 2.5 Hz, 1 H), 6.60(d, J = 8.2 Hz,1 H), 6.73(d, J = 8.2 Hz, 1 H), 6.73(dd, J = 8.2, 2.1 Hz, 1 H), 6.84 (d,J = 2.1 Hz, 1 H), 6.85- 6.90(m, 1 H), 7.16(d, J = 8.2 Hz, 1 H)

Example 25-(2-Methoxyphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Compound No. 2-1)

6-(4-Hydroxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 4-1, 25.0 mg, mmol) was dissolved in methylenedichloride (0.5 mL), triethylamine (16.2 μL, 0.116 mmol) and1-propanesulfonyl chloride (6.5 μL, 0.058 mmol) were added thereto, andthen the mixture was stirred under ice cooling for 30 minutes. Thereaction mixture was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled compound (26.8 mg) as acolorless amorphous product. (Yield 86%)

¹H-NMR (400 MHz, DMSO-d₆) δ 0.99 (t, J = 7.5 Hz, 3 H), 1.15 (s, 3 H),1.21 (s, 3 H), 1.76-1.85 (m, 2H), 2.07 (s, 3 H), 3.42- 3.46 (m, 2 H),3.68 (s, 3 H), 3.71 (s, 3 H), 3.83 (dd, J = 12.3, 3.5 Hz, 1 H), 4.00(dd, J = 12.3, 6.7 Hz, 1 H), 4.18 (dd, J = 6.7, 3.5 Hz, 1 H), 5.40 (s, 1H), 6.05 (s, 1 H), 6.33 (dd, J = 7.7, 1.3 Hz, 1 H), 6.50 (td, J = 7.7,1.3 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.66 (td, J = 7.7, 1.3 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.7, 1.3 Hz, 1 H), 6.88(dd, J = 8.1, 2.1 Hz, 1 H), 6.90 (d, J = 2.1 Hz, 1 H), 7.17 (d, J = 8.1Hz, 1 H)Using Reference Compound No. 4-1 or 4-2, the following Compounds (No.2-2˜2-11) were obtained by a method similar to that of Compound No. 2-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 1.39 (d, J =6.8 Hz, 6 H), 2.07 (s, 3 H), 3.60- 3.67 (m, 1 H), 3.69 (s, 3 H), 3.71(s, 3 H), 3.83 (dd, J = 12.6, 3.5 Hz, 1 H), 4.00 (dd, J = 12.6, 6.6 Hz,1 H), 4.18 (dd, J = 6.6, 3.5 Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H),6.33 (dd, J = 7.7, 1.3 Hz, 1 H), 6.51 (td, J = 7.7, 1.3 Hz, 1 H), 6.60(d, J = 8.2 Hz, 1 H), 6.67 (td, J = 7.7, 1.3 Hz, 1 H), 6.70 (d, J = 8.2Hz, 1 H), 6.73 (dd, J = 7.7, 1.3 Hz, 1 H), 6.87 (d, J = 2.3 Hz, 1 H),6.87 (dd, J = 8.8, 2.3 Hz, 1 H), 7.17 (d, J = 8.8 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.04 (d, J = 6.7 Hz, 6 H), 1.15 (s, 3 H),1.21 (s, 3 H), 2.07 (s, 3 H), 2.17-2.25 (m, 1 H), 3.39 (d, J = 6.7 Hz, 2H), 3.69 (s, 3 H), 3.71 (s, 3 H), 3.84 (dd, J = 12.5, 3.5 Hz, 1 H), 4.00(dd, J = 12.5, 6.6 Hz, 1 H), 4.18 (dd, J = 6.6, 3.5 Hz, 1 H), 5.40 (s, 1H), 6.04 (s, 1 H), 6.33 (dd, J = 7.8, 1.4 Hz, 1 H), 6.50 (td, J = 7.8,1.4 Hz, 1 H), 6.60 (d, J = 7.9 Hz, 1 H), 6.66 (td, J = 7.8, 1.4 Hz, 1H), 6.70 (d, J = 7.9 Hz, 1 H), 6.73 (dd, J = 7.8, 1.4 Hz, 1 H), 6.89(dd, J = 8.0, 2.4 Hz, 1 H), 6.90 (d, J = 2.4 Hz, 1 H), 7.18 (d, J = 8.0Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.07 (s, 3 H),2.88- 3.00 (m, 2 H), 3.68 (s, 3 H), 3.71 (s, 3 H), 3.80- 3.85 (m, 3 H),4.00 (dd, J = 12.2, 6.3 Hz, 1 H), 4.18 (dd, J = 6.3, 3.9 Hz, 1 H), 5.40(s, 1 H), 6.05 (s, 1 H), 6.33 (dd, J = 7.8, 1.3 Hz, 1 H), 6.50 (td, J =7.8, 1.3 Hz, 1 H), 6.61 (d, J = 8.1 Hz, 1 H), 6.66 (td, J = 7.8, 1.3 Hz,1 H), 6.70 (d, J = 8.1 Hz, 1 H), 6.73 (dd, J = 7.8, 1.3 Hz, 1 H), 6.93(dd, J = 8.1, 2.4 Hz, 1 H), 6.98 (d, J = 2.4 Hz, 1 H), 7.19 (d, J = 8.1Hz, 1 H)

¹H-NMR (500 MHz, CDCl₃) δ 1.26 (s, 3 H), 1.30 (s, 3 H), 2.19 (s, 3 H),3.01 (s, 3 H), 3.70 (s, 3 H), 3.75 (s, 3 H), 3.89 (brs, 1 H), 4.00 (d, J= 12.4 Hz, 1 H), 4.06 (d, J = 12.4 Hz, 1 H), 4.28 (s, 1 H), 5.47 (s, 1H), 6.34 (dd, J = 7.8, 1.3 Hz, 1 H), 6.56 (td, J = 7.8, 1.3 Hz, 1 H),6.56 (d, J = 7.9 Hz, 1 H), 6.68 (dd, J = 7.8, 1.3 Hz, 1 H), 6.75 (td, J= 7.8, 1.3 Hz, 1 H), 6.78 (d, J = 2.2 Hz, 1 H), 6.81 (d, J = 7.9 Hz, 1H), 6.82 (dd, J = 8.1, 2.2 Hz, 1 H), 7.18 (d, J = 8.1 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.00 (t, J = 7.5 Hz, 3 H), 1.11 (s, 3 H),1.19 (s, 3 H), 1.78-1.86 (m, 2 H), 1.88 (s, 3 H), 2.05 (s, 3 H),3.43-3.48 (m, 2 H), 3.73 (s, 3 H), 3.89 (dd, J = 13.1, 4.9 Hz, 1 H),4.07 (dd, J =13.1, 4.3 Hz, 1 H), 4.20-4.23 (m, 1 H), 5.41 (s, 1 H), 6.03(dd, J = 12.2, 2.5 Hz, 1 H), 6.04 (s, 1 H), 6.19 (td, J = 8.5, 2.5 Hz, 1H), 6.61 (d, J = 8.1 Hz, 1 H), 6.72 (d, J = 8.1 Hz, 1 H), 6.84-6.88 (m,1 H), 6.91 (dd, J = 8.2, 2.4 Hz, 1 H), 6.95 (d, J = 2.4 Hz, 1 H), 7.25(d, J = 8.2 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 0.80-1.05 (m, 4 H), 1.15 (s, 3 H), 1.22 (s,3 H), 2.09 (s, 3 H), 2.91 (tt, J = 7.9, 4.9 Hz, 1 H), 3.68 (s, 3 H),3.71 (s, 3 H), 3.81 (dd, J = 12.4, 3.4 Hz, 1 H), 3.99 (dd, J = 12.4, 6.2Hz, 1 H), 4.18 (dd, J = 6.2, 3.4 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H),6.32 (dd, J = 7.8, 1.2 Hz, 1 H), 6.50 (td, J = 7.8, 1.2 Hz, 1 H), 6.61(d, J =8.4 Hz, 1 H), 6.66 (td, J = 7.8, 1.2 Hz, 1 H), 6.71 (d, J = 8.4Hz, 1 H), 6.72 (dd, J = 7.8, 1.2 Hz, 1 H), 6.89 (dd, J = 8.2, 2.2 Hz, 1H), 6.96 (d, J = 2.2 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 1.32 (t, J =7.3 Hz, 3 H), 2.08 (s, 3 H), 3.44 (q, J = 7.3 Hz, 2 H), 3.69 (s, 3 H),3.71 (s, 3 H), 3.84 (dd, J = 12.4, 3.7 Hz, 1 H), 3.99 (dd, J = 12.4, 6.3Hz, 1 H), 4.18 (dd, J = 6.3, 3.7 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H),6.33 (dd, J = 7.8, 1.3 Hz, 1 H), 6.50 (td, J = 7.8, 1.3 Hz, 1 H), 6.60(d, J = 8.1 Hz, 1 H), 6.66 (td, J = 7.8, 1.3 Hz, 1 H), 6.70 (d, J = 8.1Hz, 1 H), 6.73 (dd, J = 7.8, 1.3 Hz, 1 H), 6.88 (dd, J = 8.2, 2.4 Hz, 1H), 6.90 (d, J = 2.4 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H)

¹H-NMR (400 MHz, DMSO-d₆) δ 0.88 (t, J = 7.3 Hz, 3 H), 1.15 (s, 3 H),1.21 (s, 3 H), 1.35-1.45 (m, 2 H), 1.72-1.80 (m, 2 H), 2.07 (s, 3 H),3.43-3.47 (m, 2 H), 3.68 (s, 3 H), 3.71 (s, 3 H), 3.84 (dd, J = 12.3,3.4 Hz, 1 H), 4.00 (dd, J = 12.3, 6.3 Hz, 1 H), 4.18 (dd, J = 6.3, 3.4Hz, 1 H), 5.40 (s, 1 H), 6.04 (s, 1 H), 6.33 (dd, J = 7.7, 1.3 Hz, 1 H),6.50 (td, J = 7.7, 1.3 Hz, 1 H), 6.60 (d, J = 8.3 Hz, 1 H), 6.66 (td, J= 7.7, 1.3 Hz, 1 H), 6.70 (d, J = 8.3 Hz, 1 H), 6.73 (dd, J = 7.7, 1.3Hz, 1 H), 6.88 (dd, J = 8.1, 2.3 Hz, 1 H), 6.90 (d, J = 2.3 Hz, 1 H),7.17 (d, J = 8.1 Hz, 1 H)

¹H-NMR (500MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 1.55-1.63 (m, 2H), 1.65-1.73 (m, 2 H), 1.92- 1.99 (m, 2 H), 2.00-2.07 (m, 2 H), 2.07(s, 3 H), 3.69 (s, 3 H), 3.71 (s, 3 H), 3.83 (dd, J = 12.7, 3.9 Hz, 1H), 3.85-3.91 (m, 1 H), 3.99 (dd, J = 12.7, 6.2 Hz, 1 H), 4.18 (dd, J =6.2, 3.9 Hz, 1 H), 5.40 (s, 1 H), 6.03 (s, 1 H), 6.33 (dd, J = 7.8, 1.2Hz, 1 H), 6.50 (td, J = 7.8, 1.2 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H),6.66 (td, J = 7.8, 1.2 Hz, 1 H), 6.70 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J= 7.8, 1.2 Hz, 1 H), 6.87 (d, J = 2.3 Hz, 1 H), 6.87 (dd, J = 8.9, 2.3Hz, 1 H), 7.17 (d, J = 8.9 Hz, 1 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.11 (s, 3 H), 1.19 (s, 3 H), 1.88 (s, 3 H),2.05 (s, 3 H), 3.34 (s, 3 H), 3.74 (s, 3 H), 3.90 (dd, J = 13.1, 4.4 Hz,1 H), 4.08 (dd, J = 13.1, 4.4 Hz, 1 H), 4.23 (t, J = 4.4 Hz, 1 H), 5.41(s, 1 H), 6.02 (dd, J = 12.2, 2.4 Hz, 1 H), 6.04 (s, 1 H), 6.19 (td, J =8.5, 2.4 Hz, 1 H), 6.61 (d, J = 8.2 Hz, 1 H), 6.72 (d, J = 8.2 Hz, 1 H),6.85-6.88 (m, 1 H), 6.92 (dd, J = 8.2, 2.3 Hz, 1 H), 7.00 (d, J = 2.3Hz, 1 H), 7.26 (d, J = 8.2 Hz, 1 H)

Example 36-(2-Methoxy-4-methoxycarbonyloxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Compound No. 3-1)

6-(4-Hydroxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 4-1, 20.0 mg, 0.0465 mmol) was dissolved inanhydrous methylene dichloride (1.0 mL), triethylamine (13 μL, 0.093mmol) and methyl chlorocarbonate (3.6 μL, 0.047 mmol) were added theretounder ice cooling, and then the mixture was stirred for 10 minutes. Thereaction mixture was purified by silica gel column chromatography(hexane-ethyl acetate) to give the titled compound (12.9 mg) as acolorless amorphous product. (Yield 57%)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H),3.65 (s, 3 H), 3.71 (s, 3 H), 3.82 (s, 3 H), 3.84 (dd, J = 12.8, 3.5 Hz,1 H), 4.01- 4.05 (m, 1 H), 4.21 (dd, J = 6.6, 3.5 Hz, 1 H), 5.39 (s, 1H), 6.00 (s, 1 H), 6.34 (dd, J = 7.8, 1.3 Hz, 1 H), 6.51 (td, J = 7.8,1.3 Hz, 1 H), 6.60 (d, J = 8.2 Hz, 1 H), 6.67 (td, J = 7.8, 1.3 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1 H), 6.73 (dd, J = 7.8, 1.3 Hz, 1 H), 6.79(dd, J = 8.2, 2.2 Hz, 1 H), 6.89 (d, J = 2.2 Hz, 1 H), 7.11 (d, J = 8.2Hz, 1 H)Using Reference Compound No. 4-1, the following Compounds (No. 3-2 and3-3) were obtained by a method similar to that of Compound No. 3-1.

¹H-NMR (400 MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.07 (s, 3 H),3.68 (s, 3 H), 3.71 (s, 3 H), 3.84 (dd, J = 12.6, 3.4 Hz, 1 H), 4.04(dd, J = 12.6, 6.5 Hz, 1 H), 4.22 (dd, J = 6.5, 3.4 Hz, 1 H), 5.39 (s, 1H), 6.02 (s, 1 H), 6.35 (dd, J = 7.9, 1.3 Hz, 1 H), 6.50 (td, J = 7.9,1.3 Hz, 1 H), 6.61 (d, J = 8.3 Hz, 1 H), 6.67 (td, J = 7.9, 1.3 Hz, 1H), 6.71 (d, J = 8.3 Hz, 1 H), 6.73 (dd, J = 7.9, 1.3 Hz, 1 H), 6.93(dd, J = 8.1, 2.4 Hz, 1 H), 7.06 (d, J = 2.4 Hz, 1 H), 7.16 (d, J = 8.1Hz, 1 H), 7.43 (d, J = 9.0 Hz, 2 H), 7.54 (d, J = 9.0 Hz, 2 H)

¹H-NMR (500 MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 1.48 (s, 9 H),2.06 (s, 3 H), 3.65 (s, 3 H), 3.71 (s, 3 H), 3.84 (dd, J = 12.0, 3.4 Hz,1 H), 4.03 (dd, J = 12.0, 6.4 Hz, 1 H), 4.22 (dd, J = 6.4, 3.4 Hz, 1 H),5.39 (s, 1 H), 6.00 (s, 1 H), 6.35 (d, J = 7.4 Hz, 1 H), 6.51 (t, J =7.4 Hz, 1 H), 6.60 (d, J = 8.1 Hz, 1 H), 6.67 (t, J = 7.4 Hz, 1 H), 6.69(d, J = 8.1 Hz, 1 H), 6.74 (d, J = 7.4 Hz, 1 H), 6.74 (dd, J = 8.2, 2.1Hz, 1 H), 6.84 (d, J = 2.1 Hz, 1 H), 7.10 (d, J = 8.2 Hz, 1 H)

Example 46-(4-Chlorophenylaminocarbonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Compound No. 4-1)

6-(4-Hydroxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 4-1, 20.0 mg, 0.0465 mmol) was dissolved inanhydrous methylene dichloride (1.0 mL), triethylamine (13 μL, 0.093mmol) and 4-chlorophenyl isocyanate (6.0 μL, 0.047 mmol) were addedthereto under ice cooling, and then the mixture was stirred for 30minutes. The reaction mixture was purified by silica gel columnchromatography (hexane-ethyl acetate) to give the titled compound (26.3mg) as a colorless amorphous product. (Yield 97%)

¹H-NMR (400 MHz, CDCl₃) δ 1.26 (s, 3 H), 1.29 (s, 3 H), 2.17 (s, 3 H),3.68 (s, 3 H), 3.75 (s, 3 H), 3.87 (brs, 1 H), 4.02 (d, J = 12.2 Hz, 1H), 4.15 (d, J = 12.2 Hz, 1 H), 4.35 (s, 1 H), 5.46 (s, 1 H), 6.39 (dd,J = 7.7, 1.6 Hz, 1 H), 6.56 (d, J = 8.2 Hz, 1 H), 6.57 (td, J = 7.7, 1.6Hz, 1 H), 6.70 (dd, J = 7.7, 1.6 Hz, 1 H), 6.70 (d, J = 2.3 Hz, 1 H),6.75 (dd, J = 8.1, 2.3 Hz, 1 H), 6.78 (td, J = 7.7, 1.6 Hz, 1 H), 6.85(d, J = 8.2 Hz, 1 H), 6.91 (s, 1 H), 7.17 (d, J =8.1 Hz, 1 H), 7.31 (d,J = 8.9 Hz, 2 H) 7.40 (d, J = 8.9 Hz, 2 H)

6-[4-[N-(2-Dimethylaminoethyl)-N-methylaminocarbonyloxy]-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline(Compound No. 4-2)

A mixture of6-(4-hydroxy-2-methoxyphenyl)-5-[N-(2-methoxyphenyl)-N-(9-fluorenylmethoxycarbonyl)aminomethyl]-2,2,4-trimethyl-1,2-dihydroquinoline(Reference Compound No. 5, 25.0 mg, 0.0383 mmol),1,1′-carbonyldiimidazole (62.0 mg, 0.382 mmol) and4-dimethylaminopyridine (0.5 mg, 0.004 mmol) was dissolved in anhydroustetrahydrofuran (1 mL), and then the solution was stirred at roomtemperature for 4.5 hours. N,N,N′-trimethylethylenediamine (39.2 mg,0.383 mmol) was added thereto, and then the mixture was stirred at 60°C. for 2 hours. The reaction mixture was purified by silica gel columnchromatography (hexane-ethyl acetate). The obtained colorless amorphousproduct was dissolved in N,N-dimethylformamide (1 mL), and thenpiperidine (50 μL) was added thereto. After the reaction mixture wasstirred at room temperature for 15 minutes, it was diluted with ethylacetate (20 mL). The mixture was washed with water (15 mL) and saturatedbrine (15 mL) successively, dried over anhydrous magnesium sulfate, andthen the solvent was removed under reduced pressure. The obtainedresidue was purified by silica gel column chromatography (hexane-ethylacetate) to give the titled compound mg) as a colorless amorphousproduct. (Yield 47%)

¹H-NMR (500MHz, DMSO-d₆) δ 1.15 (s, 3 H), 1.21 (s, 3 H), 2.06 (s, 3 H),2.17 (s, 3 H), 2.18 (s, 3 H), 2.38-2.47 (m, 2 H), 2.90, 3.02 (s, 3 H),3.33-3.38 (m, 1 H), 3.43-3.48 (m, 1 H), 3.64 (s, 3 H), 3.71 (s, 3 H),3.82-3.85 (m, 1 H), 4.05-4.06 (m, 1 H), 4.22-4.24 (m, 1 H), 5.39 (s, 1H), 5.99 (s, 1 H), 6.35 (dd, J = 7.9, 1.2 Hz, 1 H), 6.51 (td, J = 7.9,1.2 Hz, 1 H), 6.60 (d, J = 8.0 Hz, 1 H), 6.64-6.70 (m, 4 H), 6.73 (dd, J= 8.2, 1.1 Hz, 1 H), 7.06 (d, J = 8.2 Hz, 1 H)Using Reference Compound No. 4-1 or 4-2, the following Compounds (No.4-3˜4-5) were obtained by a method similar to that of Compound No. 4-1or 4-2.

¹H-NMR (400 MHz, CDCl₃) δ 1.26 (s, 3 H), 1.30 (s, 3 H), 2.17 (s, 3 H),3.68 (s, 3 H), 3.75 (s, 3 H), 3.86 (brs, 1 H), 4.03 (d, J = 12.1 Hz,1H), 4.15 (d, J = 12.1 Hz, 1 H), 4.34 (s, 1 H), 5.46 (s, 1 H), 6.39 (dd,J = 7.7, 1.4 Hz, 1 H), 6.57 (d, J = 8.1 Hz, 1 H), 6.57 (td, J = 7.7, 1.4Hz, 1 H), 6.70 (dd, J = 7.7, 1.4 Hz, 1 H), 6.71 (d, J = 2.3 Hz, 1 H),6.77 (dd, J = 8.2, 2.3 Hz, 1 H), 6.78 (td, J = 7.7, 1.4 Hz, 1 H), 6.86(d, J = 8.1 Hz, 1 H), 7.02 (s, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.30(dd, J = 8.4, 4.8 Hz, 1 H), 8.02- 8.07 (m, 1 H), 8.37 (dd, J = 4.8, 1.5Hz, 1 H), 8.57 (d, J = 2.2 Hz, 1 H)

¹H-NMR (400 MHz, CDCl₃) δ 1.24 (s, 3 H), 1.29 (s, 3 H), 1.93 (s, 3 H),2.10 (s, 3 H), 2.30 (s, 6 H), 2.53-2.58 (m, 2 H), 3.04, 3.12 (s, 3 H),3.47-3.55 (m, 2 H), 3.69 (s, 4 H), 4.09 (s, 3 H), 5.48 (s, 1 H), 6.08(dd, J = 11.7, 2.4 Hz, 1 H), 6.23 (td, J = 8.4, 2.4 Hz, 1 H), 6.58 (d, J= 8.1 Hz, 1 H), 6.70-6.75 (m, 2 H), 6.85-6.88 (m, 2 H), 7.14 (d, J = 8.1Hz, 1 H)

¹H-NMR (400 MHz, CDCl₃) δ 1.21-1.27 (m, 3 H), 1.24 (s, 3 H), 1.29 (s, 3H), 1.93 (s, 3 H), 2.10 (s, 3 H), 2.30 (s, 6 H), 2.53- 2.58 (m, 2 H),3.40-3.52 (m, 4 H), 3.70 (s, 4 H), 4.10 (s, 2 H), 5.48 (br s, 1 H), 6.08(dd, J = 11.8, 2.4 Hz, 1 H), 6.23 (td, J = 8.4, 2.4 Hz, 1 H), 6.58 (d, J= 8.1 Hz, 1 H), 6.69-6.72 (m, 1 H), 6.74 (dd, J = 8.1, 2.2 Hz, 1 H),6.84- 6.89 (m, 2 H), 7.14 (d, J = 8.1 Hz, 1 H)

PREPARATION EXAMPLES

Hereinafter, typical preparation examples of the present compound areshown.

1) Tablet (in 150 mg) Present compound 1 mg Lactose 100 mg Cornstarch 40mg Carboxymethyl cellulose calcium 4.5 mg Hydroxypropyl cellulose 4 mgMagnesium stearate 0.5 mg

A tablet of the above-mentioned formulation is coated with 3 mg of acoating agent (for example, a coating agent which is used conventionallysuch as hydroxypropylmethyl cellulose, macrogol or a silicone resin),whereby an objective tablet can be obtained. In addition, a desiredtablet can be obtained by appropriately changing the kind and/or amountof the present compound and additives.

2) Capsule (in 150 mg) Present compound 5 mg Lactose 135 mgCarboxymethyl cellulose calcium 4.5 mg Hydroxypropyl cellulose 4 mgMagnesium stearate 1.5 mg

A desired capsule can be obtained by appropriately changing the kindand/or amount of the present compound and additives.

3) Eye drop (in 100 mL) Present compound 100 mg Sodium chloride 900 mgPolysorbate 80 500 mg Sodium hydroxide q.s. Hydrochloric acid q.s.Sterile purified water q.s.

A desired eye drop can be obtained by appropriately changing the kindand/or amount of the present compound and additives.

[Pharmacological Test]

1. Evaluation Test for Binding Activity to Glucocorticoid Receptor(hereinafter referred to as “GR”)

In order to evaluate a binding activity to GR, a receptor competitorassay was carried out by a fluorescence polarization method. In theassay, a GR competitor assay kit (manufactured by Invitrogen, cat No.P2816) was used, and a procedure was carried out according to theprotocol attached to the kit. Hereinafter, the specific method will bedescribed.

(Preparation of Reagents)

GR screening buffer: A buffer containing 10 mM potassium phosphate (pH7.4), 20 mM sodium molybdate (Na₂MoO₄), 0.1 mM ethylene diaminetetraacetic acid (EDTA), 5 mM dithiothreitol (DTT), 0.1 mM stabilizingpeptide and 2% dimethylsulfoxide was prepared.

4×GS1 solution: Fluormone™ GS1, which is a fluorescent glucocorticoidligand, was diluted with GR screening buffer, whereby a 4 nM solutionwas prepared.

4×GR solution: Recombinant human GR was diluted with GR screeningbuffer, whereby a 16 nM solution was prepared.

(Preparation of Test Compound Solution)

After a test compound was dissolved in dimethylsulfoxide, the resultingsolution was diluted with GR screening buffer, whereby a 20 μM testcompound solution was prepared.

(Test Method and Measurement Method)

1) The test compound solution was added in an amount of 10 μL into eachwell of a 384-well plate, and then, 4×GS1 solution and 4×GR solutionwere added in an amount of 5 μL into each well, respectively.

2) The plate was incubated in a dark place at room temperature for 2 to4 hours.

3) By using a multimode plate reader, Analyst™ HT (manufactured by LJLBiosystems), fluorescence polarization of each well was measured. As theblank, a well containing GR screening buffer in place of the testcompound and 4×GS1 solution was used.

4) The same procedure as that in the above 1) to 3) was carried outexcept that GR screening buffer was used in place of the test compoundsolution, and the obtained result was taken as the negative control.

5) The same procedure as that in the above 1) to 3) was carried outexcept that 2 mM dexamethasone was used in place of the test compoundsolution, and the obtained result was taken as the positive control.

(Calculation Equation of GR Binding Ratio)

A GR binding ratio (%) was calculated from the following equation.

GR binding ratio (%)=100×[1−(fluorescence polarization of test compoundsolution−fluorescence polarization of positive controlsolution)/(fluorescence polarization of negative controlsolution−fluorescence polarization of positive control solution)]

(Test Results and Discussion)

As an example of the test results, the GR binding ratios (%) of the testcompounds (Compound 1-1, Compound 1-2, Compound 1-3, Compound 1-4,Compound 1-5, Compound 1-6, Compound 1-7, Compound 1-8, Compound 1-9,Compound 1-10, Compound 1-12, Compound 1-13, Compound 1-14, Compound1-15, Compound 1-16, Compound 1-17, Compound 1-18, Compound 1-22,Compound 1-23, Compound 1-26, Compound 1-27, Compound 1-28, Compound1-29, Compound 1-30, Compound 1-31, Compound 1-32, Compound 1-33,Compound 1-34, Compound 1-35, Compound 1-38, Compound 1-39, Compound1-41, Compound 1-42, Compound 1-43, Compound 1-44, Compound 1-45,Compound 2-1, Compound 2-2, Compound 2-5, Compound 2-6, Compound 2-7,Compound 2-10, Compound 2-11, Compound 4-2, Compound 4-3, Compound 4-4)are shown in Table I.

TABLE I GR Binding Test compound ratio (%) Compound 1-1 92 Compound 1-2100 Compound 1-3 95 Compound 1-4 95 Compound 1-5 93 Compound 1-6 97Compound 1-7 95 Compound 1-8 98 Compound 1-9 90 Compound 1-10 93Compound 1-12 99 Compound 1-13 100 Compound 1-14 99 Compound 1-15 99Compound 1-16 100 Compound 1-17 99 Compound 1-18 86 Compound 1-22 81Compound 1-23 86 Compound 1-26 90 Compound 1-27 87 Compound 1-28 88Compound 1-29 93 Compound 1-30 94 Compound 1-31 92 Compound 1-32 90Compound 1-33 100 Compound 1-34 100 Compound 1-35 100 Compound 1-38 100Compound 1-39 100 Compound 1-41 100 Compound 1-42 100 Compound 1-43 96Compound 1-44 96 Compound 1-45 100 Compound 2-1 100 Compound 2-2 100Compound 2-5 93 Compound 2-6 100 Compound 2-7 100 Compound 2-10 100Compound 2-11 100 Compound 4-2 98 Compound 4-3 91 Compound 4-4 100

Incidentally, in the case where the GR binding ratio of the testcompound is 100% or more, the GR binding ratio is indicated by 100%.

As is apparent from Table I, the present compound showed an excellent GRbinding activity. Accordingly, the present compound can be used as a GRmodulator, and is useful for a preventive or therapeutic agentparticularly for GR-related diseases, that is, metabolic disorders,inflammatory diseases, autoimmune diseases, allergic diseases, centralnervous system diseases, cardiovascular diseases, homeostasis-relateddiseases, glaucoma and the like.

1. A compound represented by the following general formula (1) or apharmaceutically acceptable salt thereof:

[wherein R¹ represents a hydrogen atom or a lower alkyl group; R²represents a hydrogen atom or a lower alkyl group; R³ and R⁴ may be thesame or different and represent a hydrogen atom or a lower alkyl group;R⁵ represents a hydrogen atom or a lower alkyl group; R⁶ represents ahalogen atom, a lower alkyl group, a hydroxy group, a lower alkoxygroup, a nitro group or a cyano group; X represents —CO—, —C(O)NR⁸—,—S(O)— or —S(O)₂—; R⁷ and/or R⁸ may be the same or different andrepresent a hydrogen atom, a lower alkyl group which may have asubstituent, a lower alkenyl group which may have a substituent, a loweralkynyl group which may have a substituent, a lower cycloalkyl groupwhich may have a substituent, an aryl group which may have asubstituent, a heterocyclic group which may have a substituent, a loweralkoxy group which may have a substituent, a lower alkenyloxy groupwhich may have a substituent, a lower alkynyloxy group which may have asubstituent, a lower cycloalkyloxy group which may have a substituent,an aryloxy group which may have a substituent or a heterocyclic oxygroup which may have a substituent; Y represents a lower alkylene group;p represents 0, 1, 2 or 3, in the case where p is 2 or 3, each R⁶ may bethe same or different]
 2. The compound or a pharmaceutically acceptablesalt thereof according to claim 1, wherein in the general formula (1),R¹ represents a hydrogen atom or a lower alkyl group; R² represents ahydrogen atom or a lower alkyl group; R³ and R⁴ may be the same ordifferent and represent a hydrogen atom or a lower alkyl group; R⁵represents a hydrogen atom or a lower alkyl group; R⁶ represents ahalogen atom, a lower alkyl group, a hydroxy group, a lower alkoxygroup, a nitro group or a cyano group; X represents —CO—, —C(O)NR⁸—,—S(O)— or —S(O)₂—; R⁷ and/or R⁸ may be the same or different andrepresent a hydrogen atom, a lower alkyl group, a lower alkenyl group, alower alkynyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower alkoxy group, a lower alkenyloxy group, alower alkynyloxy group, a lower cycloalkyloxy group, an aryloxy group ora heterocyclic oxy group; in the case where R⁷ and/or R⁸ is a loweralkyl group, a lower alkenyl group, a lower alkynyl group, a loweralkoxy group, a lower alkenyloxy group or a lower alkynyloxy group, thelower alkyl group, lower alkenyl group, lower alkynyl group, loweralkoxy group, lower alkenyloxy group or lower alkynyloxy group may haveone or a plurality of groups selected from a halogen atom, a lowercycloalkyl group, an aryl group, a heterocyclic group, a hydroxy group,a lower alkoxy group, a lower alkenyloxy group, a lower alkynyloxygroup, a lower cycloalkyloxy group, an aryloxy group, a heterocyclic oxygroup and —NR^(a)R^(b) as substituent(s); in the case where R⁷ and/or R⁸is a lower cycloalkyl group, an aryl group, a heterocyclic group, alower cycloalkyloxy group, an aryloxy group or a heterocyclic oxy group,the lower cycloalkyl group, aryl group, heterocyclic group, lowercycloalkyloxy group, aryloxy group or heterocyclic oxy group may haveone or a plurality of groups selected from a halogen atom, a lower alkylgroup, a halogenated lower alkyl group, an aryl group, a lower alkenylgroup, a lower alkynyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a hydroxy group, a lower alkoxy group, a halogenatedlower alkoxy group, a lower alkenyloxy group, a lower alkynyloxy group,a lower cycloalkyloxy group, an aryloxy group, a heterocyclic oxy group,a mercapto group, a lower alkylthio group, a lower alkenylthio group, alower alkynylthio group, a lower cycloalkylthio group, an arylthiogroup, a heterocyclic thio group, a lower alkylcarbonyl group, anarylcarbonyl group, a lower alkoxycarbonyl group, an aryloxycarbonylgroup, a lower alkylcarbonyloxy group, an arylcarbonyloxy group,—NR^(a)R^(b), a nitro group and a cyano group as substituent(s); R^(a)and R^(b) may be the same or different and represent a hydrogen atom, alower alkyl group, a lower alkenyl group, a lower alkynyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a loweralkoxycarbonyl group or an aryloxycarbonyl group; Y represents a loweralkylene group; p represents 0, 1, 2 or 3, in the case where p is 2 or3, each R⁶ may be the same or different.
 3. The compound or apharmaceutically acceptable salt thereof according to claim 1, whereinin the general formula (1), R¹ represents a hydrogen atom or a loweralkyl group; R² represents a hydrogen atom or a lower alkyl group; R³and R⁴ may be the same or different and represent a hydrogen atom or alower alkyl group; R⁵ represents a hydrogen atom or a lower alkyl group;R⁶ represents a halogen atom, a lower alkyl group, a hydroxy group or alower alkoxy group; X represents —CO—, —C(O)NR⁸—, —S(O)— or —S(O)₂—; R⁷and/or R⁸ may be the same or different and represent a hydrogen atom, alower alkyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower alkoxy group, a lower cycloalkyloxy group,an aryloxy group or a heterocyclic oxy group; in the case where R⁷and/or R⁸ is a lower alkyl group, the lower alkyl group may have one ora plurality of groups selected from a halogen atom and —NR^(a)R^(b) assubstituent(s); in the case where R⁷ and/or R⁸ is a lower cycloalkylgroup, an aryl group, a heterocyclic group, a lower cycloalkyloxy group,an aryloxy group or a heterocyclic oxy group, the lower cycloalkylgroup, aryl group, heterocyclic group, lower cycloalkyloxy group,aryloxy group or heterocyclic oxy group may have one or a plurality ofgroups selected from a halogen atom, a lower alkyl group, a hydroxygroup, a lower alkoxy group, a mercapto group, a lower alkylthio group,a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a loweralkylcarbonyloxy group and a nitro group as substituent(s); R^(a) andR^(b) may be the same or different and represent a hydrogen atom or alower alkyl group; Y represents a lower alkylene group; p represents 0,1, 2 or 3, in the case where p is 2 or 3, each R⁶ may be the same ordifferent.
 4. The compound or a pharmaceutically acceptable salt thereofaccording to claim 1, wherein in the general formula (1), R¹ representsa lower alkyl group; R² represents a hydrogen atom; R³ and R⁴ representa lower alkyl group; R⁵ represents a lower alkyl group; R⁶ represents ahalogen atom, a lower alkyl group or a lower alkoxy group; X represents—CO—, —C(O)NR⁸— or —S(O)₂—; R⁷ represents a lower alkyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a lower alkoxygroup or an aryloxy group; in the case where R⁷ is a lower alkyl group,the lower alkyl group may have one or a plurality of groups selectedfrom a halogen atom and —NR^(a)R^(b) as substituent(s); in the casewhere R⁷ is an aryl group, a heterocyclic group or an aryloxy group, thearyl group, heterocyclic group or aryloxy group may have one or aplurality of groups selected from a halogen atom, a lower alkyl group, alower alkoxy group, a lower alkylthio group, a lower alkylcarbonylgroup, a lower alkoxycarbonyl group, a lower alkylcarbonyloxy group anda nitro group as substituent(s); R^(a) and R^(b) may be the same ordifferent and represent a hydrogen atom or a lower alkyl group; R⁸represents a hydrogen atom or a lower alkyl group; Y represents a loweralkylene group; p represents 0, 1 or 2, in the case where p is 2, eachR⁶ may be the same or different.
 5. The compound or a pharmaceuticallyacceptable salt thereof according to claim 1, wherein in the generalformula (1), R¹ represents a lower alkyl group; R² represents a hydrogenatom; R³ and R⁴ represent a lower alkyl group; R⁵ represents a loweralkyl group; R⁶ represents a halogen atom, a lower alkyl group or alower alkoxy group; X represents —CO—, —C(O)NR⁸— or —S(O)₂—; R⁷represents a lower alkyl group, a lower cycloalkyl group, an aryl group,a heterocyclic group, a lower alkoxy group or an aryloxy group; in thecase where R⁷ is a lower alkyl group, the lower alkyl group may have oneor a plurality of groups selected from a halogen atom and —NR^(a)R^(b)as substituent(s); in the case where R⁷ is an aryl group, the aryl groupmay have one or a plurality of groups selected from a halogen atom, alower alkyl group, a lower alkoxy group, a lower alkylthio group, alower alkylcarbonyl group, a lower alkoxycarbonyl group, a loweralkylcarbonyloxy group and a nitro group as substituent(s); in the casewhere R⁷ is a heterocyclic group, the heterocyclic group may have one ora plurality of groups selected from a halogen atom, a lower alkyl groupand a lower alkoxy group as substituent(s); in the case where R⁷ is anaryloxy group, the aryloxy group may have one or a plurality of halogenatoms as substituent(s); R^(a) and R^(b) may be the same or differentand represent a hydrogen atom or a lower alkyl group; R⁸ represents ahydrogen atom or a lower alkyl group; Y represents a lower alkylenegroup; p represents 0, 1 or 2, in the case where p is 2, each R⁶ may bethe same or different.
 6. The compound or a pharmaceutically acceptablesalt thereof according to claim 1, wherein in the general formula (1),R¹, R³, R⁴ and R⁵ represent a methyl group; R² represents a hydrogenatom; Y represents a methylene group.
 7. A compound or apharmaceutically acceptable salt thereof selected from6-[4-(Furan-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Benzoyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methoxybenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(Furan-3-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiophen-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Isopropylcarbonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiophen-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(furan-2-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(4-methoxybenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(4-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methylthiobenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(3-Acetylbenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(3-Chlorothiophen-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiazol-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(6-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(furan-3-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(2-methylthiobenzoyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Dimethylaminocarbonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Isopropylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(2-Methoxy-4-methylsulfonyloxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Cyclopropylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Cyclopentylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-(2-methoxy-4-methylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-[N-(2-Dimethylaminoethyl)-N-methylaminocarbonyloxy]-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylaminocarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,and6-[4-[N-(2-Dimethylaminoethyl)-N-methylaminocarbonyloxy]-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline.8. A pharmaceutical composition, comprising the compound or apharmaceutically acceptable salt thereof according to claim 1 and apharmaceutical carrier.
 9. A modulator of glucocorticoid receptor,comprising the compound or a pharmaceutically acceptable salt thereofaccording to claim 1 as an active ingredient.
 10. A method forpreventing or treating diseases related to glucocorticoid receptor,comprising administering a pharmacologically effective amount of acompound represented by the following general formula (1) or apharmaceutically acceptable salt thereof as an active ingredient to apatient:

[wherein R¹ represents a hydrogen atom or a lower alkyl group; R²represents a hydrogen atom or a lower alkyl group; R³ and R⁴ may be thesame or different and represent a hydrogen atom or a lower alkyl group;R⁵ represents a hydrogen atom or a lower alkyl group; R⁶ represents ahalogen atom, a lower alkyl group, a hydroxy group, a lower alkoxygroup, a nitro group or a cyano group; X represents —CO—, —C(O)NR⁸—,—S(O)— or —S(O)₂—; R⁷ and/or R⁸ may be the same or different andrepresent a hydrogen atom, a lower alkyl group which may have asubstituent, a lower alkenyl group which may have a substituent, a loweralkynyl group which may have a substituent, a lower cycloalkyl groupwhich may have a substituent, an aryl group which may have asubstituent, a heterocyclic group which may have a substituent, a loweralkoxy group which may have a substituent, a lower alkenyloxy groupwhich may have a substituent, a lower alkynyloxy group which may have asubstituent, a lower cycloalkyloxy group which may have a substituent,an aryloxy group which may have a substituent or a heterocyclic oxygroup which may have a substituent; Y represents a lower alkylene group;p represents 0, 1, 2 or 3, in the case where p is 2 or 3, each R⁶ may bethe same or different].
 11. The prevention or treatment method accordingto claim 10, wherein in the general formula (1), R¹ represents ahydrogen atom or a lower alkyl group; R² represents a hydrogen atom or alower alkyl group; R³ and R⁴ may be the same or different and representa hydrogen atom or a lower alkyl group; R⁵ represents a hydrogen atom ora lower alkyl group; R⁶ represents a halogen atom, a lower alkyl group,a hydroxy group, a lower alkoxy group, a nitro group or a cyano group; Xrepresents —CO—, —C(O)NR⁸—, —S(O)— or —S(O)₂—; R⁷ and/or R⁸ may be thesame or different and represent a hydrogen atom, a lower alkyl group, alower alkenyl group, a lower alkynyl group, a lower cycloalkyl group, anaryl group, a heterocyclic group, a lower alkoxy group, a loweralkenyloxy group, a lower alkynyloxy group, a lower cycloalkyloxy group,an aryloxy group or a heterocyclic oxy group; in the case where R⁷and/or R⁸ is a lower alkyl group, a lower alkenyl group, a lower alkynylgroup, a lower alkoxy group, a lower alkenyloxy group or a loweralkynyloxy group, the lower alkyl group, lower alkenyl group, loweralkynyl group, lower alkoxy group, lower alkenyloxy group or loweralkynyloxy group may have one or a plurality of groups selected from ahalogen atom, a lower cycloalkyl group, an aryl group, a heterocyclicgroup, a hydroxy group, a lower alkoxy group, a lower alkenyloxy group,a lower alkynyloxy group, a lower cycloalkyloxy group, an aryloxy group,a heterocyclic oxy group and —NR^(a)R^(b) as substituent(s); in the casewhere R⁷ and/or R⁸ is a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower cycloalkyloxy group, an aryloxy group or aheterocyclic oxy group, the lower cycloalkyl group, aryl group,heterocyclic group, lower cycloalkyloxy group, aryloxy group orheterocyclic oxy group may have one or a plurality of groups selectedfrom a halogen atom, a lower alkyl group, a halogenated lower alkylgroup, an aryl group, a lower alkenyl group, a lower alkynyl group, alower cycloalkyl group, an aryl group, a heterocyclic group, a hydroxygroup, a lower alkoxy group, a halogenated lower alkoxy group, a loweralkenyloxy group, a lower alkynyloxy group, a lower cycloalkyloxy group,an aryloxy group, a heterocyclic oxy group, a mercapto group, a loweralkylthio group, a lower alkenylthio group, a lower alkynylthio group, alower cycloalkylthio group, an arylthio group, a heterocyclic thiogroup, a lower alkylcarbonyl group, an arylcarbonyl group, a loweralkoxycarbonyl group, an aryloxycarbonyl group, a lower alkylcarbonyloxygroup, an arylcarbonyloxy group, —NR^(a)R^(b), a nitro group and a cyanogroup as substituent(s); R^(a) and R^(b) may be the same or differentand represent a hydrogen atom, a lower alkyl group, a lower alkenylgroup, a lower alkynyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower alkoxycarbonyl group or an aryloxycarbonylgroup; Y represents a lower alkylene group; p represents 0, 1, 2 or 3,in the case where p is 2 or 3, each R⁶ may be the same or different. 12.The prevention or treatment method according to claim 10, wherein in thegeneral formula (1), R¹ represents a hydrogen atom or a lower alkylgroup; R² represents a hydrogen atom or a lower alkyl group; R³ and R⁴may be the same or different and represent a hydrogen atom or a loweralkyl group; R⁵ represents a hydrogen atom or a lower alkyl group; R⁶represents a halogen atom, a lower alkyl group, a hydroxy group or alower alkoxy group; X represents —CO—, —C(O)NR⁸—, —S(O)— or —S(O)₂—; R⁷and/or R⁸ may be the same or different and represent a hydrogen atom, alower alkyl group, a lower cycloalkyl group, an aryl group, aheterocyclic group, a lower alkoxy group, a lower cycloalkyloxy group,an aryloxy group or a heterocyclic oxy group; in the case where R⁷and/or R⁸ is a lower alkyl group, the lower alkyl group may have one ora plurality of groups selected from a halogen atom and —NR^(a)R^(b) assubstituent(s); in the case where R⁷ and/or R⁸ is a lower cycloalkylgroup, an aryl group, a heterocyclic group, a lower cycloalkyloxy group,an aryloxy group or a heterocyclic oxy group, the lower cycloalkylgroup, aryl group, heterocyclic group, lower cycloalkyloxy group,aryloxy group or heterocyclic oxy group may have one or a plurality ofgroups selected from a halogen atom, a lower alkyl group, a hydroxygroup, a lower alkoxy group, a mercapto group, a lower alkylthio group,a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a loweralkylcarbonyloxy group and a nitro group as substituent(s); R^(a) andR^(b) may be the same or different and represent a hydrogen atom or alower alkyl group; Y represents a lower alkylene group; p represents 0,1, 2 or 3, in the case where p is 2 or 3, each R⁶ may be the same ordifferent.
 13. The prevention or treatment method according to claim 10,wherein in the general formula (1), represents a lower alkyl group; R¹represents a hydrogen atom; R² and R⁴ represent a lower alkyl group; R³represents a lower alkyl group; R⁵ represents a halogen atom, a loweralkyl group or a lower alkoxy group; X represents —CO—, —C(O)NR⁸— or—S(O)₂—; R⁷ represents a lower alkyl group, a lower cycloalkyl group, anaryl group, a heterocyclic group, a lower alkoxy group or an aryloxygroup; in the case where R⁷ is a lower alkyl group, the lower alkylgroup may have one or a plurality of groups selected from a halogen atomand —NR^(a)R^(b) as substituent(s); in the case where R⁷ is an arylgroup, a heterocyclic group or an aryloxy group, the aryl group,heterocyclic group or aryloxy group may have one or a plurality ofgroups selected from a halogen atom, a lower alkyl group, a lower alkoxygroup, a lower alkylthio group, a lower alkylcarbonyl group, a loweralkoxycarbonyl group, a lower alkylcarbonyloxy group and a nitro groupas substituent(s); R^(a) and R^(b) may be the same or different andrepresent a hydrogen atom or a lower alkyl group; R⁸ represents ahydrogen atom or a lower alkyl group; Y represents a lower alkylenegroup; p represents 0, 1 or 2, in the case where p is 2, each R⁶ may bethe same or different.
 14. The prevention or treatment method accordingto claim 10, wherein in the general formula (1), R¹ represents a loweralkyl group; R² represents a hydrogen atom; R³ and R⁴ represent a loweralkyl group; R⁵ represents a lower alkyl group; R⁶ represents a halogenatom, a lower alkyl group or a lower alkoxy group; X represents —CO—,—C(O)NR⁸— or —S(O)₂—; R⁷ represents a lower alkyl group, a lowercycloalkyl group, an aryl group, a heterocyclic group, a lower alkoxygroup or an aryloxy group; in the case where R⁷ is a lower alkyl group,the lower alkyl group may have one or a plurality of groups selectedfrom a halogen atom and —NR^(a)R^(b) as substituent(s); in the casewhere R⁷ is an aryl group, the aryl group may have one or a plurality ofgroups selected from a halogen atom, a lower alkyl group, a lower alkoxygroup, a lower alkylthio group, a lower alkylcarbonyl group, a loweralkoxycarbonyl group, a lower alkylcarbonyloxy group and a nitro groupas substituent(s); in the case where R⁷ is a heterocyclic group, theheterocyclic group may have one or a plurality of groups selected from ahalogen atom, a lower alkyl group and a lower alkoxy group assubstituent(s); in the case where R⁷ is an aryloxy group, the aryloxygroup may have one or a plurality of halogen atoms as substituent(s);R^(a) and R^(b) may be the same or different and represent a hydrogenatom or a lower alkyl group; R⁸ represents a hydrogen atom or a loweralkyl group; Y represents a lower alkylene group; p represents 0, 1 or2, in the case where p is 2, each R⁶ may be the same or different. 15.The prevention or treatment method according to claim 10, wherein in thegeneral formula (1), R¹, R³, R⁴ and R⁵ represent a methyl group; R²represents a hydrogen atom; Y represents a methylene group.
 16. A methodfor preventing or treating diseases related to glucocorticoid receptor,comprising administering a pharmacologically effective amount of thecompound selected from the following compound or a Pharmaceuticallyacceptable salt thereof as an active ingredient to a patient,6-[4-(Furan-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Benzoyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methoxybenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methylbenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(Furan-3-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiophen-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Chlorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Isopropylcarbonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiophen-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(furan-2-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(3-methoxycarbonylbenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(4-methoxybenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(4-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methylthiobenzoyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(3-Acetylbenzoyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(3-Chlorothiophen-2-ylcarbonyloxy)-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(thiazol-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(6-methylpyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(furan-3-ylcarbonyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(pyridin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-(2-Fluorobenzoyloxy)-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methylpyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[4-(2-methylthiobenzoyloxy)-2-methoxyphenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(2-methoxypyridin-3-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(3-methylfuran-2-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Dimethylaminocarbonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[2-Methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-[2-methoxy-4-(morpholin-4-ylcarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Isopropylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(2-Methoxy-4-methylsulfonyloxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-(2-methoxy-4-propylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Cyclopropylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-(4-Cyclopentylsulfonyloxy-2-methoxyphenyl)-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(5-Fluoro-2-methylphenylaminomethyl)-6-(2-methoxy-4-methylsulfonyloxyphenyl)-2,2,4-trimethyl-1,2-dihydroquinoline,6-[4-[N-(2-Dimethylaminoethyl)-N-methylaminocarbonyloxy]-2-methoxyphenyl]-5-(2-methoxyphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline,5-(2-Methoxyphenylaminomethyl)-6-[2-methoxy-4-(pyridin-3-ylaminocarbonyloxy)phenyl]-2,2,4-trimethyl-1,2-dihydroquinoline,and6-[4-[N-(2-Dimethylaminoethyl)-N-methylaminocarbonyloxy]-2-methoxyphenyl]-5-(5-fluoro-2-methylphenylaminomethyl)-2,2,4-trimethyl-1,2-dihydroquinoline.17. The prevention or treatment method according to claim 11, whereinthe glucocorticoid receptor-related diseases are metabolic disorders,inflammatory diseases, autoimmune diseases, allergic diseases, centralnervous system diseases, cardiovascular diseases, homeostasis-relateddiseases and glaucoma.